Ammonium Chloride → HCID 51356692, compound

HRID 909080Notes

Reaction equation

HRID 909080 reaction equation
[Cl:1][C:2]1[C:3]([F:35])=[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](NCC(O)=O)=O)[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.C[N:46]([C:48]([O:52]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+]>CN(C)C=O>[Cl:1][C:2]1[C:3]([F:35])=[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]([CH3:25])([CH3:26])[CH3:27])[CH2:10][N:9]2[CH2:28][C:48]([NH2:46])=[O:52])[CH:5]=[CH:6][CH:7]=1

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 51356968HCID 51356968, compound

Product 1

HCID 51356692HCID 51356692, compoundYield 70.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture 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-carbonyl]-amino}-acetic acid (25.4 mg, 0.048 mmol, example 17) in N,N-dimethyl formamide (2.5 mL) was added DIPEA (44.5 mg, 0.344 mmol) and HATU (30.3 mg, 0.080 mmol). After it was stirred at rt for 22 min, ground ammonium chloride (6.6 mg, 0.12 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-2-[(2S,3S,4S)-2-(3-chloro-2-fluoro-phenyl)-3-(4-chloro-2-fluoro-phenyl)-3-cyano-4-(2,2-dimethyl-propyl)-pyrrolidin-1-yl]-acetamide (16.3 mg, 64.3%).

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-7cf1dde7485e431dbb23e0a1ac0a4c3d
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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