Aniline → HCID 67699482, compound

HRID 343192Notes

Reaction equation

HRID 343192 reaction equation
[CH:1]([N:4]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:5](=[O:30])[CH2:6][N:7]1[C:13](=[O:14])[C:12]([CH3:18])([CH2:15][CH:16]=O)[C:11](=[O:19])[N:10]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:9]2[CH:26]=[CH:27][CH:28]=[CH:29][C:8]1=2)([CH3:3])[CH3:2].[NH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.[BH3-]C#N.[Na+]>CO.C(O)(=O)C>[CH:1]([N:4]([C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1)[C:5](=[O:30])[CH2:6][N:7]1[C:13](=[O:14])[C:12]([CH3:18])([CH2:15][CH2:16][NH:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:11](=[O:19])[N:10]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:9]2[CH:26]=[CH:27][CH:28]=[CH:29][C:8]1=2)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6115AnilineHCID 5003444Sodium cyanoborohydrideHCID 86753586HCID 86753586, compound

Product 1

HCID 67699482HCID 67699482, compoundYield 76.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of 135 mg (0.28 mmol) of N-Isopropyl-2-[3-methyl-2,4-dioxo-3-(2-oxoethyl)-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-phenyl acetamide, prepared as in Intermediate 9, and 130 mg (1.40 mmol, 5.0 equiv) of aniline in 5 mL of methanol is added 18 mg (0.28 mmol, 1.0 equiv) of NaBH3CN and 1 drop of glacial acetic acid. The resulting mixture is stirred 30 min at RT, then quenched by the addition of 0.1 mL H2O and the solvent removed in vacuo. The residue is then dissolved in 40 mL of EtOAc and extracted with 0.5N HCl (1×40 mL); the organics are dried (MgSO4) and the solvent removed in vacuo. The resulting oil is purified by silica gel flash column chromatography using hexane/EtOAc 2/1 as eluent followed by further purification by reverse phase MPLC using a C-18 column and 60% acetonitrile/40% H2O with 0.1% TFA as eluent followed by lyophilization to afford 120 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz, mixture of conformational isomers) δ7.54-6.73 (m, 19H), 5.04 (m, 1H), 4.54 (d, 0.5H, J=16.6), 4.24 (m, 2H), 3.80 (d, 0.5H, J=16.6), 3.62 (m,1H), 3.34 (m, 0.5H), 2.40 (s, br, 1H), 2.05 (m, 0.5H), 1.80 (m, 0.5H), 1.62 (s, 1H), 1.12 (m, 6H); low resolution MS (FAB)m/e 561 (MH+), 468.

Workup

  1. customquenched by the addition of 0.1 mL H2O
  2. customthe solvent removed in vacuo
  3. dissolutionThe residue is then dissolved in 40 mL of EtOAc
  4. extractionextracted with 0.5N HCl (1×40 mL)
  5. dry with materialthe organics are dried (MgSO4)
  6. customthe solvent removed in vacuo
  7. customThe resulting oil is purified by silica gel flash column chromatography
  8. customfollowed by further purification by reverse phase MPLC

Sources & evidence

ORD record
ord-db716b0798514e6a861de1e0940bb698
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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