1H-Benzimidazole-2-carboxaldehyde → N-[[4-[[1H-benzimidazol-2-ylmethyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]phenyl]methyl]pyridine-2-carboxamide

HRID 970911

Reaction equation

HRID 970911 reaction equation
[N:1]1[C:10]2[CH:9]([NH:11][CH2:12][C:13]3[CH:28]=[CH:27][C:16]([CH2:17][NH:18][C:19]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=4)=[O:20])=[CH:15][CH:14]=3)[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=[C:30]1[CH:38]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[NH:29]1[C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[N:31]=[C:30]1[CH2:38][N:11]([CH2:12][C:13]1[CH:28]=[CH:27][C:16]([CH2:17][NH:18][C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[O:20])=[CH:15][CH:14]=1)[CH:9]1[C:10]2[N:1]=[CH:2][CH:3]=[CH:4][C:5]=2[CH2:6][CH2:7][CH2:8]1

Participants

4

Reactant 3

HCID 768261H-Benzimidazole-2-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10133885Pyridine-2-carboxylic acid 4-[(5,6,7,8-tetrahydro-quinolin-8-ylamino)-methyl]-benzylamide

Product 1

HCID 10185485N-[[4-[[1H-benzimidazol-2-ylmethyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]phenyl]methyl]pyridine-2-carboxamide

Procedure

Reaction of pyridine-2-carboxylic acid 4-[(5,6,7,8-tetrahydro-quinolin-8-ylamino)-methyl]-benzylamide (AMD9397) (40 mg, 0.11 mmol), 1H-benzoimidazole-2-carbaldehyde (16 mg, 0.11 mmol), and NaBH(OAc)3 (68 mg, 0.32 mmol) for 2 h at 60° C. followed by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH 198:1:1) gave AMD9401 (28 mg, 52%) as a white foam. 1H NMR (300 MHz, CD3OD) δ 1.60-1.63 (m, 1H), 1.95-2.06 (m, 2H), 2.20-2.22 (m, 1H), 2.66-2.83 (m, 2H), 3.51 (d, 1H, J=13.2 Hz), 3.58 (d, 1H, J=13.2 Hz), 3.94 (d, 1H, J=15.3 Hz), 4.04-4.09 (m, 3H), 4.42 (br s, 2H), 7.09-7.15 (m, 4H), 7.20 (dd, 1H, J=7.8, 4.8 Hz), 7.20 (d, 1H, J=8.1 Hz), 7.28 (d, 2H, J=8.1 Hz), 7.41-7.47 (m, 2H), 7.48-7.52 (m, 2H), 7.91 (ddd, 1H, J=7.5, 7.5, 1.8 Hz), 8.06 (d, 1H, J=7.8 Hz), 8.55 (d, 1H, J=4.5 Hz), 8.60 (d, 1H, J=4.5 Hz); 13C NMR (75.5 MHz, CD3OD) δ 22.84, 24.33, 30.62, 44.13, 51.41, 56.15, 63.13, 123.55, 124.03, 128.13, 128.61, 130.80, 137.39, 138.95, 139.14, 139.51, 139.67, 148.35, 150.17, 151.40, 156.31, 158.31, 166.94. ES-MS m/z 503 (M+H). Anal. Calcd. for C31H30N6O.0.8H2O.0.3CH2Cl2: C, 69.30; H, 5.98; N, 15.49. Found: C, 69.63; H, 6.14; N, 15.19.

Workup

  1. customgave AMD9401 (28 mg, 52%) as a white foam

Sources & evidence

ORD record
ord-b254f92668614437828d6ac8344980a3
Source dataset
uspto-grants-2007_12
Patent number
US07312234B2

Linked notes

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