Ammonium Chloride → Tert-butyl 1-(3-{[(4-chlorophenyl)(2,2-difluorocyclopentyl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate

HRID 1475661Notes

Reaction equation

HRID 1475661 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH:12]2[CH2:16][CH2:15][CH2:14][C:13]2([F:18])[F:17])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:19][C:20]1[CH:21]=[C:22]([CH:34]=[CH:35][C:36]=1[F:37])[CH2:23][C:24]1([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:26][CH2:25]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+]>C(#N)C.O.N1C=CC=CC=1.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([CH:12]2[CH2:16][CH2:15][CH2:14][C:13]2([F:18])[F:17])[C:9]([NH:19][C:20]2[CH:21]=[C:22]([CH:34]=[CH:35][C:36]=2[F:37])[CH2:23][C:24]2([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:25][CH2:26]2)=[O:11])=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58136688tert-Butyl 1-(3-amino-4-fluorobenzyl)cyclopropanecarboxylateHCID 58288424(4-chlorophenyl)(2,2-difluorocyclopentyl)acetic Acid

Product 1

HCID 66563456Tert-butyl 1-(3-{[(4-chlorophenyl)(2,2-difluorocyclopentyl)acetyl]amino}-4-fluorobenzyl)cyclopropanecarboxylate

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

490 mg (1.78 mmol) of (4-chlorophenyl)(2,2-difluorocyclopentyl)acetic acid (as diastereomer mixture) were added to a mixture of 4.0 ml of DMF and 1.0 ml of pyridine. At RT, 568.0 mg (2.14 mmol) of tert-butyl 1-(3-amino-4-fluorobenzyl)cyclopropanecarboxylate and 881.7 mg (2.34 mmol) of HATU were added to the resulting solution and the mixture was stirred at RT overnight. The reaction mixture was then added to saturated aqueous ammonium chloride solution and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1). Further purification of the product obtained in this manner was carried out by preparative RP-HPLC (mobile phase acetonitrile/water). This gave 774.0 mg (83.1% of theory) of the target compound.

Workup

  1. extractionextracted three times with ethyl acetate
  2. dry with materialThe combined organic phases were dried over magnesium sulphate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 20:1)
  5. customFurther purification of the product
  6. customobtained in this manner

Sources & evidence

ORD record
ord-f81ca0a8abf1458288f02dd719901b21
Source dataset
uspto-grants-2015_04
Patent number
US09018258B2

Reaction notes

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