ꢂꢁꢁꢁ
N.E. Kanitz and T. Lindel: Photoreactivity of monofluorinated 2-azidobenzimidazolesꢀ
ꢀ1299
–
19F NMR (376 MHz, [D6]DMSO): δꢀ=ꢀ–138.95. – 15N NMR (d,Jꢀ=ꢀ11.1Hz,1H,NCCHCF),6.96(d,Jꢀ=ꢀ6.9Hz,1H,7-H),6.57
(by HMBC, [D6]DMSO): δꢀ=ꢀ–322.4 (NCNH2), –303.1 (s, 2H, NH2), 4.14 (dd, Jꢀ=ꢀ6.3 Hz, Jꢀ=ꢀ8.1 Hz, 1H, NCCHCOC-
(CH2NHCOO), –264.1 (CNCH3), –187.2 (CNCNH2). – HRMS OCHCH), 3.47 (s, 3H, NCH3), 2.16 (m, 1H, CH(CH3)2), 1.42 (s,
((+)-ESI): m/zꢀ=ꢀ339.14670 (1.15 ppm, calcd. 339.14631 9H, C(CH3)3), 1.01 (d, Jꢀ=ꢀ2.7 Hz, 3H, COCOCHC(CH3)2), 1.00
+
13
for [C15H19FN4O4+H] ), 361.12832 (0.19 ppm, calcd. 361.12825 (d, Jꢀ=ꢀ2.7 Hz, 3H, COCOCHC(CH3)2). – C NMR (150 MHz,
+
for [C15H19FN4O4+Na] ), 699.26731 (0.01 ppm, calcd. [D6]DMSO): δꢀ=ꢀ170.65 (1C, COCOC(CH3)3), 156.98 (1C, C-2),
+
699.26729 for [C30H38F2N8O8+Na] ). – IR (diamond ATR): 155.85 (1C, NHCOOC(CH3)3), 149.17 (d, JCFꢀ=ꢀ234.6 Hz, 1C,
−1
ꢀ
νꢀ=ꢀ3300–3200 cm (br. w), 1686 (m), 1557 (m), 1493 (m), C-5), 140.58 (d, JCFꢀ=ꢀ11.9 Hz, 1C, C-3a), 130.79 (1C, C-7a),
1462 (m), 1287 (m), 1256 (m), 1142 (vs), 1052 (m), 1029 (m), 129.49 (d, JCFꢀ=ꢀ15.8 Hz, 1C, C-6), 101.90 (1C, C-7), 101.52 (d,
776 (m), 624 (m), 546 (m). – UV (MeOH): λmax (lg ε)ꢀ=ꢀ202 nm JCFꢀ=ꢀ21.8 Hz, 1C, C-4), 78.40 (1C, NHCOOC(CH3)3), 59.44 (1C,
(4.39), 241 (3.69), 300 (3.91).
NCCHCOCOCHNH), 29.71 (1C, NCCHCOCOCHCH(CH3)2),
28.66 (1C, NCH3), 28.19 (3C, NHCOOC(CH3)3), 18.98 (1C,
19
NCCHCOCOCHCH(CH3)2), 18.23 (1C, CH(CH3)2). – FꢀNMR
4.25 2-Amino-5-fluoro-1-methyl-1H-benzo[d]
imidazole-6-yl (tert-butoxycarbonyl)
alaninate (38)
15
(376ꢀMHz, [D6]DMSO): δꢀ=ꢀ–138.48. – N NMR (by HMBC,
[D6]DMSO): δꢀ=ꢀ–322.4 (NCNH2), –293.5 (CHNHCOO),
–264.1 (CNCH3), –186.8 (CNCNH2). – HRMS ((+)-ESI):
m/zꢀ=ꢀ381.19354 (0.73 ppm, calcd. 381.19326 for
From 22 (48 mg, 0.25 mmol 1.0 equiv.) and Boc-Ala-OH
(0.189 g, 1.00 mmol); brown solid (65 mg, 0.18 mmol, 72%).
TLC [silica, CHCl3/MeOH (10:1)]: Rfꢀ=ꢀ0.20. – [α]D23ꢀ=ꢀ–3.8 (c
+
[C18H25FN4O4+H] ), 403.17535 (0.37 ppm, calcd. 403.17520
+
for [C18H25FN4O4+Na] ), 783.36122 (0.04 ppm, calcd.
+
783.36119 for [C36H50F2N8O8+Na] ). – IR (diamond ATR):
1
1.40, DMSO). Mpꢀ=ꢀ119°C. – H NMR (600 MHz, [D6]DMSO):
−1
ꢀ
ν
ꢀ=ꢀ3340–3200 cm (br. w), 1685 (s), 1487 (m), 1460 (m),
δꢀ=ꢀ7.52 (d, Jꢀ=ꢀ7.3 Hz, 1H, COCOCHNHCO),ꢀ7.02 (d, Jꢀ=ꢀ11.0 Hz,
1H, 4-H), 7.01 (d, Jꢀ=ꢀ7.0 Hz, 1H, 7-H), 6.58 (s, 2H, NH2), 4.30
1294 (m), 1250 (m), 1140 (s), 1048 (m), 1025 (m), 780 (m),
701 (m). – UV (MeOH): λmax (lg ε)ꢀ=ꢀ202 nm (4.50), 247 (3.25),
295 (3.48).
3
(qu, Jꢀ=ꢀ7.3 Hz, 1H, NCCHCOCOCHCH3), 3.47 (s, 3H, NCH3),
13
1.43 (s, 3H, CFCOCOCHCH3), 1.41 (s, 9H, OCOC(CH3)3). – C
NMR (150 MHz, [D6]DMSO): δꢀ=ꢀ171.97 (1C, COCOC(CH3)3),
156.93 (1C, C-2), 155.28 (1C, NHCOOC(CH3)3), 149.16 (d,
JCFꢀ=ꢀ235.1 Hz, 1C, C-5), 140.45 (d, JCFꢀ=ꢀ11.7 Hz, 1C, C-4),
130.74 (1C, C-7a), 129.69 (d, JCFꢀ=ꢀ15.4 Hz, 1C, NCCHCOC-
OCH), 101.97 (1C, C-7), 101.50 (d, JCFꢀ=ꢀ21.9 Hz, 1C, C-4), 78.36
(1C, NHCOOC(CH3)3), 49.02 (1C, NCCHCOCOCHNH), 28.65
(1C, NCH3), 28.17 (3C, NHCOOC(CH3)3) 16.9 (1C, CFCOC-
OCHCH3). – 19F NMR (376 MHz, [D6]DMSO): δꢀ=ꢀ–139.22. –
15N NMR (by HMBC, [D6]DMSO): δꢀ=ꢀ–322.2 (NCNH2), –288.3
(CHNHCOO), –264.1 (CNCH3), –187.2 (CNCNH2). – HRMS
((+)-ESI): m/zꢀ=ꢀ706.31724 (0.85 ppm, calcd. 706.31664 for
4.27 2-Amino-5-fluoro-1-methyl-1H-benzo[d]
imidazole-6-yl (tert-butoxycarbonyl)-
l-phenylalaninate (40)
From 22 (46 mg, 0.24 mmol, 1.0 equiv.) and Boc-Phe-OH
(0.255 g, 0.96 mmol); red solid (59 mg, 0.14 mmol, 58%). TLC
[silica, CHCl3/MeOH (10:1)]: Rfꢀ=ꢀ0.30. – [α]D24ꢀ=ꢀ+1.9 (c 2.6,
DMSO). Mpꢀ=ꢀ81°C. – 1H NMR (600 MHz, [D6]DMSO): δꢀ=ꢀ7.57
(d, Jꢀ=ꢀ8.1 Hz, 1H, COCOCHNHCO), 7.39–7.31 (m, 5H, COC-
OCHCH2C6H5), 7.04 (d, Jꢀ=ꢀ11.0 Hz, 1H, 4-H), 6.89 (d, Jꢀ=ꢀ6.9 Hz,
1H, 7-H), 6.62 (s, 2H, NH2), 4.47 (ddd, Jꢀ=ꢀ5.0 Hz, Jꢀ=ꢀ8.1 Hz,
Jꢀ=ꢀ13.2 Hz, 1H, NCCHCOCOCHCH2), 3.47 (s, 3H, NCH3), 3.21
(dd, Jꢀ=ꢀ5.0 Hz, Jꢀ=ꢀ13.8 Hz, 1H, NCCHCOCOCHCH2Ph), 3.04
(dd, Jꢀ=ꢀ10.4 Hz, Jꢀ=ꢀ13.8 Hz, 1H, NCCHCOCOCHCH2Ph),
+
[C32H42F2N8O8+H] ), 727.29861 (0.03 ppm, calcd. 727.29859 for
+
−1
ꢀ
[C32H42F2N8O8+Na] ). – IR (diamond ATR): νꢀ=ꢀ3300–3200 cm
(br. w), 1683 (s), 1491 (m), 1462 (m), 1290 (m), 1254 (m),
1144 (s), 1050 (m), 1025 (m), 777 (m), 699 (m). – UV (MeOH):
λmax (lg ε)ꢀ=ꢀ203 nm (4.40), 242 (3.68), 299 (3.94).
13
1.35 (s, 9H, OCOC(CH3)3). – C NMR (150 MHz, [D6]DMSO):
δꢀ=ꢀ170.89 (1C, COCOC(CH3)3), 156.90 (1C, C-2), 155.50 (1C,
4.26 2-Amino-5-fluoro-1-methyl-1H-benzo[d] NHCOOC(CH3)3), 149.20 (d, JCFꢀ=ꢀ235.1 Hz, 1C, C-5), 140.40 (d,
JCFꢀ=ꢀ11.6 Hz, 1C, C-3a), 137.36 (1C, CHCOCOCHCH2C), 130.70
imidazole-6-yl (tert-butoxycarbonyl)-
(1C, C-7a), 129.62 (d, JCFꢀ=ꢀ15.7 Hz, 1C, C-6OCOCH), 129.25 (2C,
l-valinate (39)
CHCOCOCHCH2C(CH)2(CH)2), 128.29 (2C, CHCOCOCHCH2
From 22 (49 mg, 0.26 mmol, 1.0 equiv.) and Boc-Val-OH C(CH)2(CH)2), 126.60 (1C, CHCOCOCHCH2C(CH)2(CH)2CH),
2
(0.226 g, 1.04 mmol); brown solid (59 mg, 0.16 mmol, 62%). 101.90 (1C, C-7), 101.50 (d, JCFꢀ=ꢀ21.7 Hz, 1C, C-4), 78.50
[α]
TLC [silica, CHCl3/MeOH (10:1)]: Rfꢀ=ꢀ0.18. –
D23ꢀ=ꢀ–1.1 (1C, NHCOOC(CH3)3), 55.30 (1C, NCCHCOCOCHNH), 36.38
1
(c 2.3, DMSO). Mpꢀ=ꢀ63–65°C. – H NMR (600 MHz, (1C, NCCHCOCOCHCH2C), 28.70 (1C, NCH3), 28.10 (3C,
[D6]DMSO): δꢀ=ꢀ7.42 (d, Jꢀ=ꢀ8.2 Hz, 1H, COCOCHNHCO), 7.03 NHCOOC(CH3)3).–19FNMR(376MHz,[D6]DMSO):δꢀ=ꢀ–138.71.
Brought to you by | UCL - University College London
Authenticated
Download Date | 3/24/17 6:06 AM