3680-69-1

Basic information

• Product Name: 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine
• Synonyms: 4-CHLORO-1H-PYRROLO(2,3-D)PYRIMIDINE;4-CHLOROPYRROLO[2,3-D]PYRIMIDINE;4-CHLORO-7H-PYRROLO[2,3-D]PYRIMIDINE;6-CHLORO-7-DEAZAPURINE;3-d)pyrimidine,4-chloro-7h-pyrrolo(;6-CHLORO-7-DEAZAPURINE 4-CHLORO-7H-PYRROLO[2,3-D]PYRIMIDINE 4-CHLORO-1H-PYRROLO[2,3-D]PYRIMIDINE 4-CHLOROPYRROLO[2,3-D]PYRIMIDINE 6-CHLORO-7-DEAZAPURIN;4-Chloro-1H-pyrrolo[2,3-d]pyrimidine4-Chloropyrrolo[2,3-d]pyrimidine;6-Chloro-7-deazapurin
• CAS NO: 3680-69-1
• Molecular Formula: C₆H₄ClN₃
• Molecular Weight: 153.57
• EINECS: 2017-001-1
• Product Categories: Heterocycles;Heterocycles series;Halides;Pyrimidine;Heterocyclic Compounds;Biochemistry;Nucleobases and their analogs;Nucleosides, Nucleotides & Related Reagents;CHIRAL CHEMICALS;Naphthyridine,Quinoline;Bases & Related Reagents;Intermediates;Nucleotides;Fused Ring Systems;Heterocyclic Building Blocks;Heterocycle-Pyrimidine series;Baricitinib;Ruxolitinib;Tofacitinib
• Mol File: 3680-69-1.mol
• Article Data: 50

Chemical Properties

• Melting Point: 183-184°C
• Boiling Point: 325.9 °C at 760 mmHg
• Flash Point: 180.7 °C
• Appearance: White to tan/Crystalline Powder
• Density: 1.531 g/cm³
• Vapor Pressure: 0Pa at 25℃
• Storage Temp.: Room temperature.
• Solubility: Soluble in DMSO, ethyl acetate and methanol.
• PKA: 11.42±0.20(Predicted)
• CAS DataBase Reference: 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine(3680-69-1)
• EPA Substance Registry System: 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine(3680-69-1)

Safety Data

• Hazard Codes: Xi,T,Xn
• Statements: 36/37/38-25-20/21/22
• Safety Statements: 26-37-45-36
• RIDADR: UN 2811 6.1/PG 3
• WGK Germany: 3
• RTECS: UY9360000
• TSCA: No
• HazardClass: IRRITANT
• PackingGroup: Ⅲ
• Hazardous Substances Data: 3680-69-1(Hazardous Substances Data)

Usage

Uses

Different sources of media describe the Uses of 3680-69-1 differently. You can refer to the following data:
1. 4-Chloro-7H-pyrrolo[2,3-d] pyrimidine is an important pharmaceutical intermediate, which is?widely used in the synthesis of many pharmaceutical intermediates at home and abroad. Including CP690550, CGP76030 and so on, 4-Chloro-7H-pyrrolo[2,3-d] pyrimidine was the scaffold for many commercially available drugs. Also, 4-Chloro-7H-pyrrolo[2,3-d] pyrimidine was the intermediate of the bulk drug, Tofatinib, which was widely used in treatment of adult patients with moderate to severe rheumatoid arthritis with inadequate or intolerant methotrexate response.
2. 4-Chloro-7H-pyrrolo[2,3-d]pyrimidine is used in the manufacture of Tofacitinib citrate.
3. 6-Chloro-7-deazapurine is used for making tofacitinib.

Chemical Properties

Lightbrown to brown crystalline powder

Synthetic route

Allopurinol (3680-71-5) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With chlorine In 1-methyl-pyrrolidin-2-one; toluene at 160 - 180℃; Temperature;	95%
With 1,2,3-trichloropropane; chlorine In 1-methyl-pyrrolidin-2-one; toluene Reflux;	95%
With dmap; bis(trichloromethyl) carbonate In chlorobenzene at 50 - 60℃; for 6h; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;	94.2%

6-chloro-5-(2-methoxyvinyl)pyrimidin-4-ylamine → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water at 20℃; for 7.5h; Reflux;	94%
Stage #1: 6-chloro-5-(2-methoxyvinyl)pyrimidin-4-ylamine With hydrogenchloride; water In tetrahydrofuran at 20℃; Reflux; Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 1h;
With hydrogenchloride In tetrahydrofuran; water for 7.5h; Reflux;	54.5 g

7-deazahypoxanthine (3680-71-5) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With trichlorophosphate for 2h; Reflux;	93%
With trichlorophosphate	92%
With trichlorophosphate for 4h; Reflux;	91%

4-hydroxypyrrolo[2,3-D]pyrimidine → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With trichlorophosphate for 3h; Reflux;	93%

4-amino-6-chloro-5-(2,2-diethoxyethyl)pyrimidine → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With hydrogenchloride In water at 50℃; for 4h; Reagent/catalyst;	92%
With hydrogenchloride; water In Petroleum ether at 50℃; for 4h;	91%

4-amino-6-chloropyrimidine-5-acetaldehyde → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With hydrogenchloride In methanol; water at 50℃; for 3h; Concentration; Temperature; Industrial scale;	91.4%
With hydrogenchloride In methanol; water at 50 - 60℃; for 3h;	82%
With acetic acid at 20℃; for 14h;	26.1 g

1,1-dichloro-2-cyano-4-methoxy-1,3-butadiene + formamidine hydrochloride (6313-33-3) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With sodium methylate In methanol at 25 - 70℃; for 10h;	91%

1,1-dichloro-2-cyano-4-methoxy-1,3-butadiene + formamidine acetic acid (3473-63-0) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With sodium methylate In methanol at 30 - 70℃; for 10h;	90.2%

4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (123148-78-7) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With potassium benzo[d][1,3]dioxol-5-yltrifluoroborate; PdCl2(1,1'-bis(diphenylphosphino)ferrocene); triethylamine In ethanol; dichloromethane for 19h; Reagent/catalyst; Reflux;	90%

1H-pyrrolo[2,3-d]pyrimidin-4(7H)-one (3680-71-5) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With trichlorophosphate at 100℃; for 5h;	65.7%
With trichlorophosphate for 5h; Reflux;	54%
With trichlorophosphate for 5h; Reflux;	54%
With trichlorophosphate for 5h; Reflux;	54%

2-(4,6-dichloropyrimidin-5-yl)acetaldehyde (16019-33-3) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With ammonium hydroxide at 60 - 70℃; for 24h;	34%
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / ethanol / 2 h / 40 °C 2: ammonium hydroxide / ethanol / 20 h / 70 °C 3: hydrogenchloride; water / Petroleum ether / 4 h / 50 °C View Scheme
Multi-step reaction with 3 steps 1: toluene-4-sulfonic acid / ethanol / 3 h / 40 °C 2: ammonium hydroxide / 3 h / 60 °C 3: hydrogenchloride / water / 4 h / 50 °C View Scheme

ethyl 2-cyano-4,4-diethoxybutyrate (52133-67-2) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 64 percent / NaOEt 2: 92 percent / aq. HCl 3: 81 percent / H2 / Raney Ni 4: 66 percent / POCl3 View Scheme
Multi-step reaction with 3 steps 1: NaOEt / ethanol 2: 1.) Raney-Nickel; 2.) HCl 3: POCl3 View Scheme
Multi-step reaction with 4 steps 1: 64 percent / EtONa / dimethylformamide; ethanol / 6 h / Heating 2: aq. NH3 / Raney nickel / 6 h / Heating 3: 86 percent / 1N aq. HCl / 1 h / 20 °C 4: 79 percent / POCl3 / 1.5 h / Heating View Scheme

6-amino-5-(2,2-diethoxyethyl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (7400-05-7) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 92 percent / aq. HCl 2: 81 percent / H2 / Raney Ni 3: 66 percent / POCl3 View Scheme
Multi-step reaction with 3 steps 1: aq. NH3 / Raney nickel / 6 h / Heating 2: 86 percent / 1N aq. HCl / 1 h / 20 °C 3: 79 percent / POCl3 / 1.5 h / Heating View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride / water / 22 h 2: ammonium hydroxide / water / 72 h / Reflux 3: trichlorophosphate / 5 h / Reflux View Scheme
Multi-step reaction with 3 steps 1.1: hydrogenchloride / water 2.1: ammonium hydroxide / water 2.2: raney nickel / 5 h / 100 °C 3.1: trichlorophosphate / 5 h / 100 °C View Scheme

2-thioxo-1,2,3,7-tetrahydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (67831-84-9) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 81 percent / H2 / Raney Ni 2: 66 percent / POCl3 View Scheme
Multi-step reaction with 2 steps 1: ammonium hydroxide / water / 72 h / Reflux 2: trichlorophosphate / 5 h / Reflux View Scheme
Multi-step reaction with 2 steps 1.1: ammonium hydroxide / water 1.2: raney nickel / 5 h / 100 °C 2.1: trichlorophosphate / 5 h / 100 °C View Scheme

6-amino-5-(2,2-diethoxy)-2-mercaptopyrimidine-4-ol (7400-05-7) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) Raney-Nickel; 2.) HCl 2: POCl3 View Scheme
Multi-step reaction with 3 steps 1: ammonia / nickel / water / 90 °C 2: hydrogenchloride; water / 2.5 h / 20 °C 3: trichlorophosphate / 2.5 h / 100 °C View Scheme
Multi-step reaction with 3 steps 1: nickel / water / 1 h / Heating / reflux 3: trichlorophosphate / 1.5 h / Heating / reflux View Scheme

4-amino-6-hydroxy-5-(2,2-diethoxyethyl)pyrimidine (7400-06-8) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 86 percent / 1N aq. HCl / 1 h / 20 °C 2: 79 percent / POCl3 / 1.5 h / Heating View Scheme

7-deazahypoxanthine (3680-71-5) → 4-CHLORO-5,7-DIHYDRO-PYRROLO[2,3-D]PYRMIDIN-6-ONE + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With trichlorophosphate	A 49 mg (70%) B n/a

6-amino-5-(2,2-diethoxyethyl)pyrimidin-4-ol (7400-06-8) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 2.5 h / 20 °C 2: trichlorophosphate / 2.5 h / 100 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 4 h / 25 - 30 °C 2: trichlorophosphate / 1 h / 100 - 105 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride; water / 2.5 h / 20 °C 2: trichlorophosphate / 2.5 h / 100 °C View Scheme
Multi-step reaction with 2 steps 2: trichlorophosphate / 1.5 h / Heating / reflux View Scheme

6-amino-5-(2,2-diethoxyethyl)-2-mercaptopyrimidin-4-ol → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: ammonia / water / 90 °C 2: hydrogenchloride / water / 2.5 h / 20 °C 3: trichlorophosphate / 2.5 h / 100 °C / Inert atmosphere View Scheme

6-chloro-5-((trimethylsilyl)ethynyl)pyrimidin-4-amine (1615680-91-5) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
With 1-methyl-pyrrolidin-2-one; potassium tert-butylate at 90℃; for 0.833333h;	505 mg

5-allyl-4,6-dichloropyrimidine (16019-31-1) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: ammonium hydroxide / ethanol / 24 h / 60 °C / Industrial scale 2: ozone / methanol / -30 °C / Industrial scale 3: hydrogenchloride / methanol; water / 3 h / 50 °C / Industrial scale View Scheme
Multi-step reaction with 2 steps 1: ozone / methanol; dichloromethane / 2 h / -40 °C 2: ammonium hydroxide / 24 h / 60 - 70 °C View Scheme
Multi-step reaction with 3 steps 1: ammonium hydroxide / ethanol / 24 h / 70 °C / Sealed tube 2: triethylamine; dimethyl sulfoxide; ozone / methanol / 2 h / -5 - 0 °C 3: acetic acid / 14 h / 20 °C View Scheme

2-cyano-4,4-dimethoxybutyric acid ethyl ester (773076-83-8) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium ethanolate / ethanol / Reflux 2: hydrogenchloride / water / 45 °C 3: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 50 °C View Scheme

6-amino-5-(2,2-dimethoxyethyl)pyrimidin-4-ol → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 45 °C 2: trichlorophosphate; N-ethyl-N,N-diisopropylamine / toluene / 50 °C View Scheme

5-(prop-2-en-1-yl)pyrimidine-4,6-diol (16019-30-0) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: N,N-dimethyl-aniline; trichlorophosphate / acetonitrile / 3 h / 80 °C / Inert atmosphere 2: ozone / methanol; dichloromethane / 2 h / -40 °C 3: ammonium hydroxide / 24 h / 60 - 70 °C View Scheme
Multi-step reaction with 4 steps 1: N,N-dimethyl-aniline; trichlorophosphate / acetonitrile / 3 h / 80 °C / Inert atmosphere 2: ammonium hydroxide / ethanol / 24 h / 70 °C / Sealed tube 3: triethylamine; dimethyl sulfoxide; ozone / methanol / 2 h / -5 - 0 °C 4: acetic acid / 14 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1: N,N-dimethyl-aniline; trichlorophosphate / acetonitrile / 3 h / 80 °C / Inert atmosphere 2: ozone / methanol; dichloromethane / 2 h / -40 °C 3: toluene-4-sulfonic acid / ethanol / 2 h / 40 °C 4: ammonium hydroxide / ethanol / 20 h / 70 °C 5: hydrogenchloride; water / Petroleum ether / 4 h / 50 °C View Scheme

4,6-dichloro-5-(2,2-diethoxyethyl)pyrimidine (14052-82-5) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: ammonium hydroxide / ethanol / 20 h / 70 °C 2: hydrogenchloride; water / Petroleum ether / 4 h / 50 °C View Scheme

dimethyl allylmalonate (40637-56-7) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium methylate / methanol / 5 h / 0 - 60 °C 2: N,N-dimethyl-aniline; trichlorophosphate / acetonitrile / 3 h / 80 °C / Inert atmosphere 3: ozone / methanol; dichloromethane / 2 h / -40 °C 4: ammonium hydroxide / 24 h / 60 - 70 °C View Scheme
Multi-step reaction with 5 steps 1: sodium methylate / methanol / 5 h / 0 - 60 °C 2: N,N-dimethyl-aniline; trichlorophosphate / acetonitrile / 3 h / 80 °C / Inert atmosphere 3: ammonium hydroxide / ethanol / 24 h / 70 °C / Sealed tube 4: triethylamine; dimethyl sulfoxide; ozone / methanol / 2 h / -5 - 0 °C 5: acetic acid / 14 h / 20 °C View Scheme
Multi-step reaction with 6 steps 1: sodium methylate / methanol / 5 h / 0 - 60 °C 2: N,N-dimethyl-aniline; trichlorophosphate / acetonitrile / 3 h / 80 °C / Inert atmosphere 3: ozone / methanol; dichloromethane / 2 h / -40 °C 4: toluene-4-sulfonic acid / ethanol / 2 h / 40 °C 5: ammonium hydroxide / ethanol / 20 h / 70 °C 6: hydrogenchloride; water / Petroleum ether / 4 h / 50 °C View Scheme

2-mercapto-4-hydroxy-7H-pyrrolo[2,3-d]pyrimidine (67831-84-9) → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide; dihydrogen peroxide / water / 2 h / 15 - 20 °C 2: hydrogenchloride / water / 1 h 3: trichlorophosphate / 85 °C View Scheme

C10H19N3O3S → 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 20 °C / pH 2 - 3 2: sodium hydroxide; dihydrogen peroxide / water / 2 h / 15 - 20 °C 3: hydrogenchloride / water / 1 h 4: trichlorophosphate / 85 °C View Scheme

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) + methylamine (74-89-5) → 4-(methylamino)-7H-pyrrolo<2,3-d>pyrimidine (78727-16-9)

Conditions	Yield
In ethanol at 100℃; for 2h; Sealed tube;	100%
With hydrogenchloride In methanol for 6h; Heating;	85%

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine (123148-78-7)

Conditions	Yield
With N-iodo-succinimide; sodium sulfate In ethanol; N,N-dimethyl-formamide	100%
With N-iodo-succinimide; sodium sulfate In ethanol; N,N-dimethyl-formamide	100%
With N-iodo-succinimide; sodium sulfate In ethanol; N,N-dimethyl-formamide	100%

(5-(methoxycarbonyl)-1-tosyl-1H-pyrrol-3-yl)boronic acid (916177-00-9) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1-(toluene-4-sulfonyl)-1H-pyrrole-2-carboxylic acid methyl ester

Conditions	Yield
With potassium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane; water at 170℃; for 0.166667h; Microwave irradiation;	100%

4-tert-butoxycarbonylamino-piperidine-4-carboxylic acid ethyl ester (956460-98-3) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-tert-butoxycarbonylamino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidine-4-carboxylic acid ethyl ester (956460-97-2)

Conditions	Yield
With triethylamine In 1-methyl-pyrrolidin-2-one at 110℃; for 68h;	100%
With triethylamine In 1-methyl-pyrrolidin-2-one at 110℃; for 68h;	100%
With triethylamine In 1-methyl-pyrrolidin-2-one at 110℃; for 68h;	100%

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-chloro-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidine (870706-50-6)

Conditions	Yield
Stage #1: 4-chloro-1H-pyrrolo[2,3-d]pyrimidine With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 5.5h; Stage #2: With water; ammonium chloride In tetrahydrofuran; hexane	100%

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-iodo-7H-pyrrolo[2,3-d]pyrimidine (1100318-96-4)

Conditions	Yield
With hydrogen iodide In water at 20℃; for 80h; Inert atmosphere;	100%
With hydrogen iodide at 20℃; for 80h; Inert atmosphere;	98%
With hydrogen iodide In water at 20℃; for 48h;	91%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrole[2,3-d]pyrimidine (941685-26-3)

Conditions	Yield
Stage #1: 4-chloro-1H-pyrrolo[2,3-d]pyrimidine With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1h; Cooling with ice; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-formamide Cooling with ice;	100%
Stage #1: 4-chloro-1H-pyrrolo[2,3-d]pyrimidine With sodium hydride In N,N-dimethyl-formamide at 20℃; for 1h; Cooling with ice; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-formamide for 1h; Cooling with ice;	100%
Stage #1: 4-chloro-1H-pyrrolo[2,3-d]pyrimidine With sodium hydride In N,N-dimethyl-formamide; mineral oil at 10℃; for 1h; Cooling with ice; Inert atmosphere; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-formamide; mineral oil at 10 - 20℃;	97%

triisopropylsilyl chloride (13154-24-0) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-chloro-7-triisopropylsilanyl-7H-pyrrolo[2,3-d]pyrimidine (870706-50-6)

Conditions	Yield
Stage #1: 4-chloro-1H-pyrrolo[2,3-d]pyrimidine With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: triisopropylsilyl chloride In tetrahydrofuran; hexane at -78 - 20℃; for 4.5h; Inert atmosphere;	100%
Stage #1: 4-chloro-1H-pyrrolo[2,3-d]pyrimidine With sodium hydride In tetrahydrofuran; mineral oil at 0 - 6.8℃; for 0.916667h; Inert atmosphere; Stage #2: triisopropylsilyl chloride In tetrahydrofuran; mineral oil at 0℃; for 4h; Inert atmosphere; Reflux;	99%

1H-pyrazolo[3,4-b]pyridin-5-amine (942185-01-5) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → N-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-5-amine

Conditions	Yield
With hydrogenchloride In ethanol; water for 6h; Reflux;	100%

(+/-)-cis-4-methyl-1-(phenylmethyl)-piperidin-3-ylamine + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → cis-1-benzyl-4-methyl-N-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}piperidin-3-amine

Conditions	Yield
With potassium carbonate In water at 100℃; for 48h; Sealed tube;	100%

(R)-piperidin-3-ylcarbamic acid tert-butyl ester (309956-78-3) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → (R)-tert-butyl (1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-3-yl)carbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In butan-1-ol at 80℃; for 52h; Inert atmosphere; Sealed tube;	100%

tert-butyl N-methyl-N-[(3R,4R)-4-methylpiperidin-3-yl]carbamate + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → C18H27N5O2

Conditions	Yield
With potassium carbonate In 1,4-dioxane; water at 100℃; for 10h;	100%

(R)-N-methyl-5-((R)-1-phenylethyl)-5-azaspiro[2.4]heptan-7-amine + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → N-methyl-N-((R)-5-((R)-1-phenylethyl)-5-azaspiro[2.4]heptan-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine

Conditions	Yield
With potassium carbonate In water for 18h; Reflux;	100%

benzyl (3S,4R)-3-methyl-1,6-diazaspiro[3.4]octane-1-carboxylate oxalate + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → benzyl (3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]octane-1-carboxylate

Conditions	Yield
With potassium phosphate In ethanol; water at 40 - 80℃; for 5h; Inert atmosphere;	100%
With potassium phosphate In ethanol; water at 80℃; for 5h; Inert atmosphere;
With potassium phosphate In ethanol; water at 80℃; for 5h; Temperature; Inert atmosphere;

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 5-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (22276-95-5)

Conditions	Yield
With N-Bromosuccinimide In acetonitrile at 100℃; for 0.166667h; microwave irradiation;	99%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃; for 12h;	95%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃; for 72h;	95%

N-methylcyclohexylamine (100-60-7) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → N-cyclohexyl-N-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine (252722-30-8)

Conditions	Yield
In 1,4-dioxane at 110℃; for 9h; Microwave irradiation; Sealed tube;	99%
Stage #1: N-methylcyclohexylamine; 4-chloro-1H-pyrrolo[2,3-d]pyrimidine In tert-butyl alcohol at 100℃; for 24h; Stage #2: With hydrogenchloride In water; tert-butyl alcohol pH=1; Stage #3: With sodium hydroxide In water; tert-butyl alcohol pH=14;	88%
In tert-butyl alcohol at 85℃;

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) + 1-t-Butoxycarbonylpiperazine (57260-71-6) → 4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboxylic acid tert-butyl ester

Conditions	Yield
With RuPhos palladacycle; lithium hexamethyldisilazane; ruphos In tetrahydrofuran at 65℃; for 4h; Inert atmosphere; Sealed vial;	99%
With triethylamine In butan-1-ol at 90℃;	74%
With triethylamine In N,N-dimethyl-formamide at 110℃; for 16h;	59%

tert-butyl 3-(cyanomethyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate (1153949-15-5) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 1,1-dimethylethyl 3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-1-azetidinecarboxylate

Conditions	Yield
With [1,1′-bis(di-cyclohexylphosphino)ferrocene]dichloro palladium(II); cesium fluoride In water; tert-butyl alcohol Suzuki Coupling; Inert atmosphere; Reflux;	99%
With [1,1′-bis(di-cyclohexylphosphino)ferrocene]dichloropalladium (II); cesium fluoride In water; tert-butyl alcohol Inert atmosphere; Reflux;	99%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water for 1h; Reflux;

2-(1-(ethanesulfonyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-3-yl)acetonitrile + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → Baricitinib (1187594-09-7)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 80 - 85℃; for 5h;	99%
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In water; toluene; tert-butyl alcohol at 100℃; for 48h; Concentration; Temperature; Solvent; Reagent/catalyst; Suzuki Coupling; Inert atmosphere;	90%
With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In tetrahydrofuran; water at 90℃; for 19h; Autoclave; Inert atmosphere;	90%
With tetrakis(triphenylphosphine) palladium(0); cesium fluoride In water; toluene; tert-butyl alcohol for 48h; Suzuki Coupling; Reflux; Inert atmosphere;	84%

tributylphenylstannane (960-16-7) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-phenyl-7H-pyrrolo[2,3-d]pyrimidine (1168106-39-5)

Conditions	Yield
With 1,8-Cineole; bis-triphenylphosphine-palladium(II) chloride; triphenyl-arsane at 100℃; for 32h; Stille Cross-Coupling (Migita-Kosugi-Stille Coupling);	99%

t-butyl (3S,4R)-3-methyl-1,6-diazaspiro[3.4]octane-1-carboxylate + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → t-butyl (3S,4R)-3-methyl-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]octane-1-carboxylate

Conditions	Yield
With potassium carbonate In water at 110℃; for 4h;	99%

Chloromethyl pivalate (18997-19-8) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → (4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)methyl 2,2-dimethylpropanoate (1146629-75-5)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 14h;	98.85%
Stage #1: 4-chloro-1H-pyrrolo[2,3-d]pyrimidine With sodium hydride In tetrahydrofuran at 0 - 20℃; Inert atmosphere; Stage #2: Chloromethyl pivalate In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	91%
Stage #1: 4-chloro-1H-pyrrolo[2,3-d]pyrimidine With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Inert atmosphere; Stage #2: Chloromethyl pivalate In tetrahydrofuran; mineral oil at 0 - 20℃; Product distribution / selectivity; Inert atmosphere;	91%

benzenesulfonyl chloride (98-09-9) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-chloro-7-(phenylsulfonyl)-7H-pyrrolo [2,3-d]pyrimidine (186519-89-1)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 0 - 20℃;	98%
With sodium hydride at 0 - 25℃; for 4h;	98%
With sodium t-butanolate In tetrahydrofuran at 10 - 22℃; for 2h;	92%

piperidine (110-89-4) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 4-(piperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine (94581-94-9)

Conditions	Yield
With silver trifluoromethanesulfonate In N,N-dimethyl-formamide at 90℃;	98%
With potassium hydroxide In water at 100℃; under 750.075 Torr; for 0.166667h; Microwave irradiation;	84%
In tert-butyl alcohol at 85℃; for 3h;	60%
In tert-butyl alcohol at 100℃; for 0.166667h; Microwave irradiation;

3-chloro-4-fluorophenylamine (367-21-5) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → (3-chloro-4-fluoro-phenyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (346600-33-7)

Conditions	Yield
With silver trifluoromethanesulfonate In N,N-dimethyl-formamide at 90℃;	98%

2-fluoro-4-chloroaniline (57946-56-2) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → (4-chloro-2-fluoro-phenyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (865364-20-1)

Conditions	Yield
With silver trifluoromethanesulfonate In N,N-dimethyl-formamide at 90℃;	98%

3-acetylenephenylamine (54060-30-9) + 4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → (3-ethynyl-phenyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (186519-85-7)

Conditions	Yield
With silver trifluoromethanesulfonate In N,N-dimethyl-formamide at 90℃;	98%

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) → 7H-pyrrolo[2,3-d]pyrimidine (271-70-5)

Conditions	Yield
With hydrogen; palladium 10% on activated carbon In methanol under 760.051 Torr; for 16h;	98%
With ammonium formate; 20% Pd(OH)2 on carbon In methanol for 2h; Heating / reflux;	97%
With hydrogen; palladium on activated charcoal	84%
With ammonium hydroxide; hydrogen; palladium on activated charcoal In ethanol at 20℃; for 6h;	83.7%
With hydrogen; palladium 10% on activated carbon In methanol at 20℃;

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) + p-toluenesulfonyl chloride (98-59-9) → 4-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidine (479633-63-1)

Conditions	Yield
With sodium hydroxide In water; acetone at 0 - 20℃; for 6h;	97%
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 0.5h; Large scale;	97.7%
With dmap; triethylamine In dichloromethane at 0 - 20℃; Industrial scale;	97.7%

4-chloro-1H-pyrrolo[2,3-d]pyrimidine (3680-69-1) + methyl iodide (74-88-4) → 4-Chlor-7-methyl-7H-pyrrolo<2,3-d>pyrimidin (7781-10-4)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 20℃; for 4h;	97%
With caesium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 1h;	94%
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 6h;	88%

Upstream product

• 3680-71-5 7-deazahypoxanthine 
• 16019-31-1 5-allyl-4,6-dichloropyrimidine 
• 773076-83-8 2-cyano-4,4-dimethoxybutyric acid ethyl ester 
• 463-52-5 formamidine 
• 6313-33-3 formamidine hydrochloride 
• 3473-63-0 formamidine acetic acid 
• 67831-84-9 2-mercapto-4-hydroxy-7H-pyrrolo[2,3-d]pyrimidine 
• 40637-56-7 dimethyl allylmalonate 
• 14052-82-5 4,6-dichloro-5-(2,2-diethoxyethyl)pyrimidine 
• 16019-33-3 2-(4,6-dichloropyrimidin-5-yl)acetaldehyde 
• 16019-30-0 5-(prop-2-en-1-yl)pyrimidine-4,6-diol 
• 1615680-91-5 6-chloro-5-((trimethylsilyl)ethynyl)pyrimidin-4-amine 
• 123148-78-7 4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine 
• 7400-06-8 6-amino-5-(2,2-diethoxyethyl)pyrimidin-4-ol 

Downstream Products

• 384337-90-0 methyl(1-phenylmethyl-4-methylpiperidin-3-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine 
• 69-33-0 tubercidin 
• 16754-80-6 4-chloro-7-(β-D-ribofuranosyl)-7H-pyrrolo<2,3-d>pyrimidine 
• 905581-58-0 4-phenethyl-7H-pyrrolo[2,3-d]pyrimidine 
• 186519-91-5 4-chloro-7-allyl-pyrrolo[2,3-d]pyrimidine 
• 22276-95-5 5-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidine 
• 908283-37-4 benzyl 1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,2-dihydro-1'H-spiro[indole-3,4'-piperidine]-1'-carboxylate 
• 78727-16-9 C₇H₈N₄ 
• 1005206-16-5 7H-pyrrolo[2,3-d]pyrimidine-4-carbonitrile 
• 1040918-30-6 C₃₂H₃₆ClN₃O₃Si 
• 1035387-04-2 4-(5-(4-methoxyphenoxy)-1H-benzoimidazol-2-yl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amine 
• 1035390-77-2 benzyl (4-(4-phenyl-1H-benzo[d]imidazol-2-yl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-yl)methylcarbamate 
• 1035346-02-1 ethyl 4-((diphenylmethyleneamino)methyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylate 
• 1035346-15-6 4-((diphenylmethyleneamino)methyl)-1-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)piperidine-4-carboxamide 

Relevant articles and documents

Synthesis and biological evaluation of some new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidine derivatives as potential antitubercular agents

A series of new tricyclic pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidines 8a–l were synthesized and characterized by IR, NMR (1H and 13C), and mass spectral analysis. The newly synthesized compounds 8a–l were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis (MTB) H37Ra using an established XTT reduction menadione assay (XRMA). The title compounds exhibited minimum inhibitory concentrations (MIC90) ranging from 0.09 to >30 μg/mL. Five compounds (8c, 8i–l) were further confirmed for their dose-dependent effect against MTB. These compounds were evaluated in the THP-1 infection model, where 8i (MIC90 = 0.35 μg/mL), 8j (MIC90 = 1.17 μg/mL), 8k (MIC90 = 2.38 μg/mL), and 8l (MIC90 = 1.17 μg/mL) demonstrated significant antitubercular activity. All the ex vivo active compounds showed insignificant cytotoxicity against the human cancer cell lines, HeLa, MCF-7, and THP-1. Inactivity of all these compounds against Gram positive and Gram negative bacteria indicates their specificity. Molecular docking studies in the active site of the sterol 14alpha-demethylase (CYP51) enzyme revealed a similar binding mode to the native ligand in the crystal structure, thereby helping to understand the ligand–protein interactions and to establish a structural basis for inhibition of MTB. The results suggest novel pharmacophores as selective and specific inhibitors against MTB that can be explored further to synthesize lead compounds against tuberculosis. In summary, the results clearly indicate the identification of some novel, selective, and specific inhibitors against MTB that can be explored further for potential antitubercular drugs.

Production system of medical intermediate 4-chloropyrrolopyrimidine

The invention discloses a production system of medical intermediate 4-chloropyrrolopyrimidine. The production system is used for a novel production process of 4-chloropyrrolopyrimidine by taking pyrrolo[2,3-d]pyrimidin-4-ol as a reaction substrate, and comprises a high-temperature and high-pressure stirring reaction kettle for preparing 4-chloropyrrolopyrimidine by taking pyrrolo[2,3-d]pyrimidin-4-ol as a substrate; the top of the high-temperature and high-pressure stirring reaction kettle is connected with an alkali liquor pool for absorbing tail gas through a pipeline with a valve; the bottom of the high-temperature and high-pressure stirring reaction kettle is connected with a distillation tower used for evaporating a solvent through a pipeline; the distillation tower is connected witha condenser used for condensing solvent steam and a washing kettle used for washing an obtained product; the condenser is connected with a solvent recovery tank used for recovering the solvent; and the washing kettle is connected with a suction filtration barrel used for separating a solid product. Because a large amount of POCl3 does not need to be used in a new production method, the quenching process is safe, the whole set of device is closed, little toxic gas is discharged, and the purpose of green production can be achieved.

Method for preparing 4-chloro-7H-pyrrolo[2,3-d]pyrimidine by adopting non-phosphorus chlorination reagent

The invention discloses a method for preparing 4-chloro-7H-pyrrolo[2,3-d]pyrimidine from a non-phosphorus chlorination reagent, which is technically characterized by comprising the following steps: 1)preparing a Vilsmeier reagent from a non-phosphorus reagent and N,N-dimethylformamide (DMF) in an aprotic solvent; and 2) adding 4-hydroxy-7H-pyrrolo[2,3-d]pyrimidine into the prepared Vilsmeier reagent, and carrying out a chlorination reaction to generate the 4-chloro-7H-pyrrolo[2,3-d]pyrimidine. The objective of the invention is to provide the method for preparing the 4-chloro-7H-pyrrolo[2,3-d]pyrimidine by using the non-phosphorus chlorination reagent. A large amount of phosphorus-containing waste liquid in the production process can be avoided.