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New Journal of Chemistry
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Journal Name
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2',3',8',9',12',13'-hexahydro-7'H,11'H-spiro[cyclohexane-1,4'-
pyrido[3,2,1-ij]pyrido[4',3':4,5]pyrano[2,3-f]quinolin]-5'(1'H)-
DOI: 10.1039/D0NJ02664F
Hz, 3H), 7.45 (d, J = 8.8 Hz, 1H), 6.61 (dd, J = 8.8, 2.2 Hz, 1H),
one 2,2,2-trifluoroacetate in 2 mL of dichloromethane at 0°C 6.40 (d, J = 2.2 Hz, 1H), 6.26 (s, 2H), 3.13-2.93 (m, 2H), 2.76-2.57
was added 51 mg (0.51 mmol, 2.2 eq) of triethylamine followed (m, 2H), 1.97-1.78 (m, 2H), 1.78-1.72 (m, 1H), 1.71-1.56 (m, 3H),
by 22 mg (0.28 mmol, 1.2 eq) of acetyl chloride. The mixture 1.57-1.43 (m, 6H), 1.44-1.03 (m, 8H), 0.97 (s, 3H), 0.95-0.74 (m,
was stirred at 25oC for 2 h, poured into water, and extracted 4H), 0.70 (s, 3H). Calcd for C30H41N2O2 [MH+]: 461.3163. Found:
with dichloromethane. The organic layers were dried over 461.3167.
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anhydrous MgSO4 and concentrated. The product was purified (4R,5'S,8'S,9'S,10'S,13'S,14'S)-8-(Dimethylamino)-10',13'-
by chromatography using 1:20 methanol-dichloromethane (Rf = dimethyl-1',2,2',3,4',5',6',7',8',9',10',11',12',13',14',15',16',17'-
0.37 after two developments) to provide 59 mg of 11ec (63%). octadecahydrospiro[chromeno[3,4-c]pyridine-4,3'-
1H NMR (400 MHz, CDCl3) δ 6.83 (s, 1H), 3.81 (t, J = 6.2 Hz, 2H), cyclopenta[a]phenanthren]-5(1H)-one hydrochloride (11bg).
3.29-3.17 (m, 4H), 2.84 (q, J = 6.7 Hz, 4H), 2.74 (t, J = 6.4 Hz, 2H), Condition C: yield 70%; purified by trituration with hot
2.67-2.53 (m, 4H), 2.24 (s, 3H), 2.06-1.9 (m, 4H), 1.77-1.62 (m, methanol. 1H NMR (400 MHz, CF3COOD) δ 7.96 (d, J = 8.8 Hz,
2H), 1.51-1.38 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 173.15, 1H), 7.87 (br. s, 1H), 7.77 (d, J = 2.3 Hz, 1H), 7.73 (dd, J = 8.9, 2.1
160.01, 149.92, 146.37, 145.21, 123.36, 120.58, 118.01, 108.62, Hz, 1H), 3.86-3.69 (m, 2H), 3.45 (s, 6H), 3.11 (t, J = 13.8 Hz, 1H),
106.3, 62.36, 50.01, 49.66, 39.76, 33.83, 27.97, 26.71, 25.42, 2.94 (t, J = 13.9 Hz, 1H), 1.98-1.9 (m, 1H), 1.9-1.77 (m, 2H), 1.72
25.41, 22.56, 21.86, 20.9, 20.46. HRMS (ESI) calcd for (d, J = 12.6 Hz, 1H), 1.67-1.48 (m, 5H), 1.47-1.32 (m, 5H), 1.32-
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C25H31N2O3 [MH+]: 407.2329. Found: 407.2314.
2,2',3,3',5',6',8,9,12,13-Decahydro-7H,11H-spiro[pyrido[3,2,1- 0.78 (dt, J = 11.7, 11, 3.8 Hz, 1H), 0.69 (s, 3H). 13C NMR (100
ij]pyrido[4',3':4,5]pyrano[2,3-f]quinoline-4,4'-thiopyran]- MHz, CF3COOD) δ 162.54, 154.54, 149.99, 146.98, 129.77,
5(1H)-one 2,2,2-Trifluoroacetate (11ee). Condition B: mp > 126.7, 122.58, 120.00, 111.85, 64.46, 56.5, 49.28, 43.36, 42.64,
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C; yield 81%. 1H NMR (400 MHz, DMSO-d6) δ 9.7 (br. s, 41.94, 40.43, 38.2, 37.98, 37.9, 35.14, 34.58, 33.80, 29.71,
1.23 (m, 3H), 1.22-1.1 (m, 3H), 1.09 (s, 3H), 1.04-0.87 (m, 2H),
2H), 7.15 (s, 1H), 3.44-3.33 (m, 2H), 3.26 (q, J = 6.1 Hz, 4H), 3.19 28.46, 26.96, 25.12, 22.68, 21.76, 18.15, 12.68. HRMS (ESI)
(t, J = 13.2 Hz, 2H), 3.09 (t, J = 6.2 Hz, 2H), 2.93 (td, J = 14.3, 4 Calcd for C32H45N2O2 [MH+]: 489.3476. Found: 489.3478.
Hz, 2H), 2.73 (q, J = 6.9 Hz, 4H), 2.57-2.48 (m, 2H), 2.15 (br. d, J (3R,5S,8S,9S,10S,13S,14S)-10,13-Dimethyl-1,2,2',3',4,5,6,7,
= 14.6 Hz, 2H), 1.87 (q, J = 5.4, 5 Hz, 4H). 13C NMR (100 MHz, 8,8',9,9',10,11,12,12',13,13',14,15,16,17-docosahydro-
DMSO-d6) δ 158.49, 149.32, 147.75, 145.72, 121.7, 118.47, 7'H,11'H-spiro[cyclopenta[a]phenanthrene-3,4'-pyrido[3,2,1-
106.25, 104.71, 64.91, 49.17, 48.66, 34.51, 30.23, 27.09, 21.32, ij]pyrido[4',3':4,5]pyrano[2,3-f]quinolin]-5'(1'H)-one
20.9, 19.99, 19.72, 15.17. HRMS (ESI) Calcd for C22H27N2O2S hydrochloride (11eg). Condition C: yield 86%; purified by
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[MH+]: 383.1788. Found: 383.1791.
8-(Dimethylamino)-1'-methyl-2,3-dihydrospiro[chromeno-
trituration with hot methanol. H NMR (400 MHz, CF3COOD) δ
7.98-7.43 (m, 1H), 3.94-3.69 (m, 6H), 3.5 (t, J = 6.2 Hz, 2H), 3.25
[3,4-c]pyridine-4,4'-piperidin]-5(1H)-one (11bf). Condition B: (t, J = 6.9 Hz, 4H), 3.05 (t, J = 13.7 Hz, 1H), 2.61-2.41 (m, 4H),
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C; yield 73%. H NMR (400 MHz, DMSO-d6) δ 7.48 (d, 2.03 (d, J = 14 Hz, 1H), 1.98-1.86 (m, 2H), 1.81 (d, J = 12.6 Hz,
J = 9.2 Hz, 1H), 6.72 (dd, J = 9, 2.4 Hz, 1H), 6.49 (d, J = 2.4 Hz, 1H), 1.77-1.57 (m, 5H), 1.57-1.43 (m, 5H), 1.43-1.31 (m, 3H), 1.3-
1H), 3 (s, 6H), 2.9 (t, J = 6.8 Hz, 2H), 2.73-2.66 (m, 4H), 2.62-1.58 1.2 (m, 3H), 1.19 (s, 3H), 1.12-0.96 (m, 2H), 0.87 (dt, J = 12.3,
(m, 4H), 2.3 (s, 3H), 1.36 (d, J = 12.4 Hz, 2H). 13C NMR (100 MHz, 11.8, 4.5 Hz, 1H), 0.79 (s, 3H). 13C NMR (100 MHz, CF3COOD) δ
DMSO-d6) δ 159.22, 153.86, 152.16, 150.31, 125.05, 122.14, 162.99, 150.42, 150.15, 137.1, 131.52, 126.21, 123.77, 121.25,
109.1, 108.67, 96.71, 50.97, 49.93, 44.9, 35.8, 30.32, 26. HRMS 64.47, 56.55, 56.27, 43.42, 42.67, 41.98, 40.47, 38.29, 38, 37.94,
(ESI) Calcd for C19H26N3O2 [MH+]: 328.2020. Found: 328.2023. 35.25, 34.63, 33.84, 29.74, 28.5, 27, 26.84, 25.12, 22.71, 21.8,
1-Methyl-2',3',8',9',12',13'-hexahydro-7'H,11'H-
spiro[piperidine-4,4'-pyrido[3,2,1-
21.55, 21.36, 20.57, 18.19, 12.7. HRMS (ESI) Calcd for
C36H49N2O2 [MH+]: 541.3789. Found: 541.3790.
ij]pyrido[4',3':4,5]pyrano[2,3-f]quinolin]-5'(1'H)-one (11ef). (3R,5S,8S,9S,10S,13S,14S)-10,13-Dimethyl-
Condition B: mp = 144-146 C (decomp); yield 84%; 1,2',3',4,5,6,7,8,8',9,9',10,11,12,12',13,13',14,15,16-
chromatographic solvent: 1:10 methanol-dichloromethane (Rf icosahydro-7'H,11'H-spiro[cyclopenta[a]phenanthrene-3,4'-
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0.13). H NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 7.1 (s, 1H), pyrido[3,2,1-ij]pyrido[4',3':4,5]pyrano[2,3-f]quinoline]-
3.31-3.11 (m, 8H), 2.9 (t, J = 6.6 Hz, 2H), 2.84 (dt, J = 14.8, 13.8, 5',17(1'H,2H)-dione (11eh). Condition C: yield 57%. 1H NMR
4.5 Hz, 2H), 2.76 (s, 3H), 2.75-2.69 (m, 4H), 2.67 (t, J = 5.6 Hz, (400 MHz, DMSO-d6) δ 7.04 (s, 1H), 3.21 (q, J = 5.5 Hz, 4H), 2.85
2H), 2.02-1.8 (m, 4H), 1.6 (d, J = 14.2 Hz, 2H). 13C NMR (100 (t, J = 5.8 Hz, 2H), 2.71 (q, J = 6.1 Hz, 4H), 2.58 (t, J = 5.7 Hz, 2H),
MHz, DMSO-d6) δ 159.5, 157.92, 157.62, 151.09, 149.26, 2.46-2.3 (m, 3H), 2.08-1.95 (m, 1H), 1.93-1.78 (m, 5H), 1.74 (dd,
145.05, 121.32, 119.13, 118.87, 118.03, 115.87, 107.72, 104.82, J = 12.7, 3.3 Hz, 1H), 1.7-1.59 (m, 2H), 1.59-1.42 (m, 3H), 1.4-
49.96, 49.16, 48.66, 35.97, 27.12, 25.74, 21.05, 20.17, 19.83. 1.32 (m, 2H), 1.31-1.18 (m, 4H), 1.18-1.08 (m, 3H), 1.02-0.96 (m,
HRMS (ESI) Calcd for C23H30N3O2 [MH+]: 380.2333. Found: 1H), 0.95 (s, 3H), 0.79 (s, 3H), 0.79-0.7 (m, 1H). 13C NMR (100
380.2337.
MHz, DMSO-d6) δ 219.89, 159.52, 149.46, 149.08, 144.61,
122.46, 121.13, 117.71, 108.15, 104.87, 53.87, 53.64, 50.83,
49.16, 48.66, 47.14, 36.12, 35.77, 35.32, 34.63, 33.23, 31.45,
30.65, 28.01, 27.8, 27.12, 26.28, 21.38, 21.15, 20.27, 19.86,
(4R,5'S,8'S,9'S,10'S,13'S,14'S)-8-Amino-10',13'-dimethyl-
1',2,2',3,4',5',6',7',8',9',10',11',12',13',14',15',16',17'-
octadecahydrospiro[chromeno[3,4-c]pyridine-4,3'-
cyclopenta[a]phenanthren]-5(1H)-one (11ag). Condition C:
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