Acetic Acid → HCID 12003959, compound

HRID 2245867Notes

Reaction equation

HRID 2245867 reaction equation
[CH2:1]([O:3][C:4](=[O:38])[CH2:5][CH2:6][N:7]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:37])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C@@H:21]([N:29]3[CH2:34][C@@H:33]([CH3:35])[NH:32][CH2:31][C@@H:30]3[CH3:36])[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=3)[CH:16]=2)[CH2:9][CH2:8]1)[CH3:2].[CH:39](=O)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:38])[CH2:5][CH2:6][N:7]1[CH2:13][CH2:12][CH2:11][N:10]([C:14](=[O:37])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C@@H:21]([N:29]3[CH2:34][C@@H:33]([CH3:35])[N:32]([CH2:39][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[CH2:31][C@@H:30]3[CH3:36])[C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=3)[CH:16]=2)[CH2:9][CH2:8]1)[CH3:2]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58815867HCID 58815867, compound

Product 1

HCID 12003959HCID 12003959, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound of Example 11 (560 mg), benzaldehyde (227.4 mg) and acetic acid (128.6 mg) in DMF was stirred under nitrogen at room temperature for 30 minutes. Na(OAc)3BH (568 mg) was added to the solution. The reaction was stirred under nitrogen at room temperature for overnight. The reaction was quenched by the addition of saturated NH4Cl solution (1 mL), followed by the addition of H2O (80 mL) for the attempt of making organic product crashed out of water layer. The solution was cloudy but no solid was formed. The solution was extracted by EtOAc (40 mL×3). The combined organic layer was washed by water (50 mL×2) and brine (50 mL×1), dried by Na2SO4 and concentrated to give crude product (466 mg), which was purified by silica gel chromatography conducted on CombiFlash™ Sq 16× (gradient: 100% CH2Cl2 to 10% MeOH in CH2Cl2) to give 3-(4-{3-[(R)-((2S,5R)-4-benzyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-[1,4]diazepan-1-yl)-propionic acid ethyl ester as white solid (290 mg; 44%). 1H NMR (300 MHz, CDCl3) δ 7.59-7.45 (m, 1H), 7.40 - 7.22 (m, 8H), 7.13 (dd, 1H, J=7.0, 7.0 Hz), 6.71 (m, 3H), 5.08 (s, 1H), 4.16 (q, 2H, J=7.0 Hz), 3.98 (m, 1H), 3.70 (m, 2H), 3.35 (m, 2H), 3.25 (m, 1H), 2.84 (m, 3H), 2.66 (m, 6H), 2.47 (m, 3H), 2.11 (m, 2H), 1.93 (m, 1H), 1.70 (m, 1H), 1.27 (t, 3H, J=7.0 Hz), 1.13 (bs, 3H), 1.06 (d, 3H, J=5.5 Hz).

Workup

  1. customThe reaction was quenched by the addition of saturated NH4Cl solution (1 mL)
  2. additionfollowed by the addition of H2O (80 mL) for the attempt of making organic product
  3. customno solid was formed
  4. extractionThe solution was extracted by EtOAc (40 mL×3)
  5. washThe combined organic layer was washed by water (50 mL×2) and brine (50 mL×1)
  6. dry with materialdried by Na2SO4
  7. concentrationconcentrated
  8. customto give crude product (466 mg), which
  9. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-2bdcdd95716f4607b6eaf8fd988ed4aa
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

Loading…