Ammonium Chloride → HCID 75631466, compound

HRID 909072Notes

Reaction equation

HRID 909072 reaction equation
[Cl:1][C:2]1[C:3]([F:37])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][N:9]2[C:28]([NH:30][CH2:31][CH2:32][CH2:33][C:34]([OH:36])=O)=[O:29])[CH:5]=[CH:6][CH:7]=1.CC[N:40](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+]>CN(C)C=O>[C:34]([CH2:33][CH2:32][CH2:31][NH:30][C:28]([N:9]1[CH2:10][CH:11]([CH2:23][C:24]([CH3:25])([CH3:26])[CH3:27])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[F:22])([C:13]#[N:14])[CH:8]1[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[F:37])=[O:29])(=[O:36])[NH2:40]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 51356415HCID 51356415, compound

Product 1

HCID 75631466HCID 75631466, compoundYield 85.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture rac-4-{[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carbonyl]-amino}-butyric acid (22.7 mg, 0.041 mmol, Example C11) in N,N-dimethyl formamide (2.5 mL) was added DIPEA (37.1 mg, 0.287 mmol) and HATU (25.1 mg, 0.066 mmol). After it was stirred at rt for 35 min, ground ammonium chloride (5.1 mg, 0.095 mmol,) was added. After 3 hrs the reaction mixture was extracted with EtOAc, and washed with water, 10% ammonium chloride, saturated sodium bicarbonate, water, and saturated NaCl. The organic phase was separated, and dried over Na2SO4. The reaction mixture was then purified by flash column to give rac-(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidine-1-carboxylic acid (3-carbamoyl-propyl)-amide (19.4 mg, 85.6%). HRMS (ES+) m/z Calcd for C27H30Cl2F2N4O2+Na [(M+Na): 573.1606; Found: 573.1609.

Workup

  1. extractionAfter 3 hrs the reaction mixture was extracted with EtOAc
  2. washwashed with water, 10% ammonium chloride, saturated sodium bicarbonate, water, and saturated NaCl
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. customThe reaction mixture was then purified by flash column

Sources & evidence

ORD record
ord-2cf02f3502bb4372884154d162503d05
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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