Acetic Acid → HCID 12003960, compound

HRID 2245869Notes

Reaction equation

HRID 2245869 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].[F:39][C:40]1[CH:41]=[C:42]([CH:45]=[CH:46][CH:47]=1)[CH:43]=O.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]([CH2:43][C:42]4[CH:45]=[CH:46][CH:47]=[C:40]([F:39])[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 680093-FluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58815867HCID 58815867, compound

Product 1

HCID 12003960HCID 12003960, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The solution of 3-(4-{3-[(R)-((2S,5R)-2,5-Dimethyl-piperazin-1-yl)-(3-hydroxy-methyl]-benzoyl}-[1,4]diazepan-1-yl)-propionic acid ethyl ester (288 mg; Example 11), 3-fluorobenzaldehyde (137 mg) and acetic acid (66 mg) in DMF (3 mL) was stirred under nitrogen at room temperature for 20 minutes, followed by the addition of Na(OAc)3BH (292 mg). The reaction was stirred under nitrogen at room temperature for overnight. The reaction was quenched by the addition of H2O (4 mL). The solution was neutralized by sat. NaHCO3 solution to pH≅7. The solution was extracted by EtOAc (5 mL×3). The combined organic layer was washed by water (5 mL×2) and brine (5 mL×1), dried by Na2SO4 and concentrated to give crude product (300 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-(3-Fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-(3-hydroxy-phenyl)-methyl]-benzoyl}-[1,4]diazepan-1-yl)-propionic acid ethyl ester as white solid (120 mg; 35%). 1H NMR (300 MHz, CDCl3) δ 7.59-7.48 (m, 1H), 7.40-7.22 (m, 4H), 7.16-7.04 (m, 3H), 6.92 (m, 1H), 6.72 (m, 3H), 5.04 (bs, 1H), 4.15 (q, J=7.0 Hz, 2H), 3.92 (m, 1H), 3.77 (m, 1H), 3.71 (m, 1H), 3.43 (m, 1H), 3.35 (m, 1H), 3.24 (m, 1H), 2.94-2.81 (m, 3H), 2.72-2.44 (m, 9H), 2.05 (m, 2H), 1.96 (m, 1H), 1.75 (bs, 1H), 1.26 (t, J=7.0 Hz, 3H), 1.06 (m, 6H).

Workup

  1. customThe reaction was quenched by the addition of H2O (4 mL)
  2. extractionThe solution was extracted by EtOAc (5 mL×3)
  3. washThe combined organic layer was washed by water (5 mL×2) and brine (5 mL×1)
  4. dry with materialdried by Na2SO4
  5. concentrationconcentrated
  6. customto give crude product (300 mg), which
  7. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-672ea0ac27ce47268700f32145894b22
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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