Diisopropylethylamine → 4-[(S)-3-(t-butoxycarbonylamino)-2-oxopyrrolidin-1-ylmethyl]-3-trifluoromethyl-N-{4-methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]phenyl}benzamide

HRID 13793

Reaction equation

HRID 13793 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][C:16]=2[C:24]([F:27])([F:26])[F:25])[C:10]1=[O:28])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.[CH3:71][C:72]1[CH:78]=[CH:77][C:75]([NH2:76])=[CH:74][C:73]=1[NH:79][C:80]1[N:85]=[C:84]([C:86]2[CH:87]=[N:88][CH:89]=[N:90][CH:91]=2)[CH:83]=[CH:82][N:81]=1>CN(C)C=O.O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:23]=[CH:22][C:18]([C:19]([NH:76][C:75]3[CH:77]=[CH:78][C:72]([CH3:71])=[C:73]([NH:79][C:80]4[N:85]=[C:84]([C:86]5[CH:91]=[N:90][CH:89]=[N:88][CH:87]=5)[CH:83]=[CH:82][N:81]=4)[CH:74]=3)=[O:21])=[CH:17][C:16]=2[C:24]([F:25])([F:27])[F:26])[C:10]1=[O:28])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 231458394-Methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]anilineHCID 686918124-[(S)-3-(t-butoxycarbonylamino)-2-oxopyrrolidin-1-ylmethyl]-3-trifluoromethylbenzoic acid

Product 1

HCID 686943924-[(S)-3-(t-butoxycarbonylamino)-2-oxopyrrolidin-1-ylmethyl]-3-trifluoromethyl-N-{4-methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]phenyl}benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Eight hundred mg of 4-[(S)-3-(t-butoxycarbonylamino)-2-oxopyrrolidin-1-ylmethyl]-3-trifluoromethylbenzoic acid (Reference Example 17) was dissolved in 7 ml of anhydrous N,N-dimethylformamide, and 0.67 ml of N,N-diisopropyl-N-ethylamine and 1.00 g of 1H-benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) were added in turn, followed by stirring at room temperature for 30 minutes. 4-Methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]aniline (Reference Example 18) was added and the mixture was stirred at room temperature for 18 hours. The reaction solution was diluted with water, followed by extraction with ethyl acetate. The organic layer was washed in turn with an aqueous saturated sodium hydrogen carbonate solution and water, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography to obtain 453 mg of the objective compound as a pale yellow amorphous.

Workup

  1. stirringthe mixture was stirred at room temperature for 18 hours
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed in turn with an aqueous saturated sodium hydrogen carbonate solution and water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-62c7d4eb7c2a488594f16c5174ac8846
Source dataset
uspto-grants-2010_06
Patent number
US07728131B2

Linked notes

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