Diisopropylethylamine → HCID 67095667, compound

HRID 909073Notes

Reaction equation

HRID 909073 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.C[CH2:39][N:40](C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.CN>CN(C)C=O>[CH3:39][NH:40][C:34]([CH2:33][CH2:32][CH2:31][NH:30][C:28]([N:9]1[CH2:10][CH:11]([CH2:23][C:24]([CH3:26])([CH3:27])[CH3:25])[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]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 6364545Methylamine hydrochlorideHCID 51356415HCID 51356415, compound

Product 1

HCID 67095667HCID 67095667, compoundYield 94.6%

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 (24.0 mg, 0.043 mmol, Example 58) in N,N-dimethyl formamide (2.5 mL) was added DIPEA (48.2 mg, 0.373 mmol), HoBt (12.2 mg, 0.090 mmol), HBTU (30.7 mg, 0.081 mmol) and methylamine hydrochloride (9.6 mg, 0.142 mmol). After it was stirred at rt for 5.5 hrs, the solvent was removed and the reaction mixture was extracted with EtOAc, and washed with 1N sodium hydroxide (2×), 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-methylcarbamoyl-propyl)-amide (23.0 mg, 93.7%). HRMS (ES+) m/z Calcd for C28H32Cl2F2N4O2+H [(M+H)+]: 565.1943; Found: 565.1944.

Workup

  1. customthe solvent was removed
  2. extractionthe reaction mixture was extracted with EtOAc
  3. washwashed with 1N sodium hydroxide (2×), water, and saturated NaCl
  4. customThe organic phase was separated
  5. dry with materialdried over Na2SO4
  6. customThe reaction mixture was then purified by flash column

Sources & evidence

ORD record
ord-0b9948687eb142298943119fdf554f27
Source dataset
uspto-grants-2011_09
Patent number
US08017607B2

Reaction notes

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