Sodium Hydroxide → HCID 68283299, compound

HRID 1527400Notes

Reaction equation

HRID 1527400 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@:11]([F:24])([CH2:13][N:14]([CH3:23])[C:15]([O:17][CH2:18][C:19]([Cl:22])([Cl:21])[Cl:20])=[O:16])[CH2:10][C@H:9]1[C:25](=[O:36])NCC1C=CC=C(Cl)C=1F)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl[C:40]1[C:41](F)=[C:42]([CH2:46]N)[CH:43]=[CH:44][CH:45]=1.CN(C([O:56]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.O.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@:11]([F:24])([CH2:13][N:14]([CH3:23])[C:15]([O:17][CH2:18][C:19]([Cl:20])([Cl:22])[Cl:21])=[O:16])[CH2:10][C@H:9]1[C:25]([O:56][CH2:46][C:42]1[CH:43]=[CH:44][CH:45]=[CH:40][CH:41]=1)=[O:36])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2773614(3-Chloro-2-fluorophenyl)methanamineHCID 86673845HCID 86673845, compound

Product 1

HCID 68283299HCID 68283299, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S,4S)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-fluoro-4-{[methyl-(2,2,2-trichloro-ethoxycarbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (110 mg, 0.20 mmol) in methanol (5 mL), 1M sodium hydroxide 0.40 mL, 0.40 mmol) was added. The solution was stirred for 2 h at RT then was diluted with water, the methanol was removed under reduced pressure. The aqueous layer was washed with Et2O (2×25 mL). The aqueous layer was acidified until pH 3 with 2N HCl and extracted with EtOAc (2×25 mL), dried with Na2SO4, filtered and concentrated. To the residue (80 mg, 0.17 mmol), (3-chloro-2-fluorophenyl)methanamine (33.9 mg, 0.21 mmol) and HBTU (101 mg, 0.26 mmol) dissolved in DMF (5 mL) was added DIPEA (0.06 mL, 0.35 mmol). The reaction mixture was stirred for 16 h at RT. The reaction mixture was quenched with water, extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography on silica gel (c-hexane/EtOAc 1:1). MS (UPLC/MS): 592/594 [M+H]+, 636/638 [M+HCOO]−; tR (HPLC conditions f): 2.49 min.

Workup

  1. customthe methanol was removed under reduced pressure
  2. washThe aqueous layer was washed with Et2O (2×25 mL)
  3. extractionextracted with EtOAc (2×25 mL)
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. stirringThe reaction mixture was stirred for 16 h at RT
  8. customThe reaction mixture was quenched with water
  9. extractionextracted with EtOAc
  10. washwashed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customPurification by flash column chromatography on silica gel (c-hexane/EtOAc 1:1)
  15. custom2.49 min.

Sources & evidence

ORD record
ord-8726199cacfb4a52bc4300fed310971f
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

Loading…