Lithium borohydride → 1-{2-[(2S,4R)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-6-(2-hydroxy-ethoxy)-1H-indole-3-carboxylic acid amide

HRID 1527575Notes

Reaction equation

HRID 1527575 reaction equation
C[O:2][C:3](=O)[CH2:4][O:5][C:6]1[CH:14]=[C:13]2[C:9]([C:10]([C:36](=[O:38])[NH2:37])=[CH:11][N:12]2[CH2:15][C:16]([N:18]2[CH2:22][C@H:21]([F:23])[CH2:20][C@H:19]2[C:24](=[O:35])[NH:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([Cl:33])[C:28]=2[F:34])=[O:17])=[CH:8][CH:7]=1.[Li+].[BH4-]>C1COCC1>[Cl:33][C:29]1[C:28]([F:34])=[C:27]([CH:32]=[CH:31][CH:30]=1)[CH2:26][NH:25][C:24]([C@@H:19]1[CH2:20][C@@H:21]([F:23])[CH2:22][N:18]1[C:16](=[O:17])[CH2:15][N:12]1[C:13]2[C:9](=[CH:8][CH:7]=[C:6]([O:5][CH2:4][CH2:3][OH:2])[CH:14]=2)[C:10]([C:36]([NH2:37])=[O:38])=[CH:11]1)=[O:35]

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 68283320(3-Carbamoyl-1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-1H-indol-6-yloxy)-acetic acid methyl ester

Product 1

HCID 682838691-{2-[(2S,4R)-2-(3-Chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-6-(2-hydroxy-ethoxy)-1H-indole-3-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3-carbamoyl-1-{2-[(2S,4R)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-pyrrolidin-1-yl]-2-oxo-ethyl}-1H-indol-6-yloxy)-acetic acid methyl ester Example 592 (30.0 mg, 0.049 mmol) in THF (1 mL) was added LiBH4 (2M in THF; 0.049 mL, 0.098 mmol) and stirring was continued at RT for 2 h. The reaction mixture was partitioned between CH2Cl2 and water, and the aqueous layer was extracted with CH2Cl2 (3×). The combined organics were dried (phase separator) and concentrated under reduced pressure. Purification by preparative HPLC (SunFire C18-ODB, 5 μm, 19×50 mm, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 20 mL/min) afforded after lyophilization of the purified fractions the desired compound as a white solid. MS: 535 [M+H]+; tR (HPLC conditions c): 3.72 min.

Workup

  1. customThe reaction mixture was partitioned between CH2Cl2 and water
  2. extractionthe aqueous layer was extracted with CH2Cl2 (3×)
  3. customThe combined organics were dried (phase separator)
  4. concentrationconcentrated under reduced pressure
  5. customPurification by preparative HPLC (SunFire C18-ODB, 5 μm, 19×50 mm, eluent: 5-100% CH3CN/H2O/20 min, 100% CH3CN/2 min, CH3CN and H2O containing 0.1% TFA, flow: 20 mL/min)
  6. customafforded after lyophilization of the
  7. custompurified fractions the desired compound as a white solid
  8. custom3.72 min.

Sources & evidence

ORD record
ord-d2f2ca6cd8e644fdbd40f054d3b18ac9
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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