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

HRID 970929

Reaction equation

HRID 970929 reaction equation
[N:1]1[C:10]2[CH:9]([NH:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)=[O:21])=[CH:15][CH:14]=3)[CH2:8][CH2:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[NH:28]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=[C:29]1[CH:37]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>>[NH:28]1[C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=2[N:30]=[C:29]1[CH2:37][N:11]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[O:21])=[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 10269770Pyridine-2-carboxylic acid {4-[(5,6,7,8-tetrahydro-quinolin-8-ylamino)-methyl)-phenyl}-amide

Product 1

HCID 10184809N-[4-[[1H-benzimidazol-2-ylmethyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]phenyl]pyridine-2-carboxamide

Procedure

Using general procedure B: Reaction of pyridine-2-carboxylic acid {4-[(5,6,7,8-tetrahydro-quinolin-8-ylamino)-methyl]-phenyl}-amide (AMD9409) (67 mg, 0.19 mmol), 1H-benzoimidazole-2-carbaldehyde (30 mg, 0.21 mmol), and NaBH(OAc)3 (119 mg, 0.50 mmol) for 0.5 h at 60° C. followed by purification of the crude product by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH 198:1:1) gave AMD9413 (48 mg, 53%) as a white foam. 1H NMR (300 MHz, CDCl3) δ 1.62-1.75 (m, 1H), 1.96-2.07 (m, 2H), 2.23-2.30 (m, 1H), 2.68-2.91 (m, 2H), 3.74 (br s, 2H), 3.98 (d, 1H, J=16.8 Hz), 4.09 (m, 1H), 4.19 (d, 1H, J=16.5 Hz), 7.16-7.20 (m, 3H), 7.41-7.46 (m, 4H), 7.53 (d, 1H, J=6.0 Hz), 7.64-7.67 (m, 3H), 7.87 (ddd, 1H, J=7.5, 7.5, 1.5 Hz), 8.26 (d, 1H, J=7.8 Hz), 8.58 (d, 1H, J=3.9 Hz), 8.70 (d, 1H, J=3.3 Hz), 9.94 (br s, 1H); 13C NMR (75.5 MHz, CDCl3) δ 21.39, 23.41, 29.22, 48.54, 53.54, 60.11, 119.57, 121.50, 122.25, 122.36, 126.37, 129.28, 134.71, 135.33, 136.73, 137.21, 137.62, 146.93, 147.93, 149.80, 157.47, 161.84. ES-MS m/z 489 (M+H). Anal. Calcd. for C30H28N6O.0.5H2O.0.3CHCl3: C, 68.23; H, 5.54; N, 15.76. Found: C, 68.06; H, 5.54; N, 15.46.

Workup

  1. customfollowed by purification of the crude product by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH 198:1:1)
  2. customgave AMD9413 (48 mg, 53%) as a white foam

Sources & evidence

ORD record
ord-83959091195d48f7acfd8d7d987d69ab
Source dataset
uspto-grants-2007_12
Patent number
US07312234B2

Linked notes

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