Benzoyl Peroxide → Methyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-methyl-6-(3-(trifluoromethyl)phenylamino)pyrimidine-5-carboxylate

HRID 711422Notes

Reaction equation

HRID 711422 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([CH3:22])[C:19]([C:23]([O:25][CH3:26])=[O:24])=[C:18](NC2C=C(C)C=CC=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:35][C:36]([F:45])([F:44])[C:37]1[CH:38]=[C:39]([CH:41]=[CH:42][CH:43]=1)[NH2:40].[Br:46]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@H:10]1[NH:15][C:16]1[N:21]=[C:20]([CH3:22])[C:19]([C:23]([O:25][CH3:26])=[O:24])=[C:18]([NH:40][C:39]2[CH:41]=[CH:42][CH:43]=[C:37]([C:36]([F:44])([F:45])[F:35])[CH:38]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:46][CH2:22][C:20]1[C:19]([C:23]([O:25][CH3:26])=[O:24])=[C:18]([NH:40][C:39]2[CH:41]=[CH:42][CH:43]=[C:37]([C:36]([F:44])([F:45])[F:35])[CH:38]=2)[N:17]=[C:16]([NH:15][C@@H:10]2[CH2:11][CH2:12][CH2:13][CH2:14][C@@H:9]2[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[N:21]=1

Participants

7

Reactant 4

HCID 7187Benzoyl PeroxideHCID 73753-(Trifluoromethyl)anilineHCID 67184N-bromobutanimideHCID 67238015Methyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-methyl-6-(m-tolylamino)pyrimidine-5-carboxylate

Product 2

HCID 67238282Methyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-methyl-6-(3-(trifluoromethyl)phenylamino)pyrimidine-5-carboxylateHCID 67238407Methyl 4-(bromomethyl)-2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-6-(3-(trifluoromethyl)phenylamino)pyrimidine-5-carboxylate

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Conditions

Temperature
70 °C

Procedure

Methyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-methyl-6-(3-(trifluoromethyl)phenylamino)pyrimidine-5-carboxylate (104 mg, 0.199 mmol), which was prepared in a manner similar to methyl 2-((1R,2S)-2-(tert-butoxycarbonyl-amino)cyclohexylamino)-4-methyl-6-(m-tolylamino)pyrimidine-5-carboxylate in step B of EXAMPLE 1 using 3-(trifluoromethyl)aniline in place of m-toluidine in step A of the example, was combined with 1-bromopyrrolidine-2,5-dione (53.0 mg, 0.298 mmol) and benzoic peroxyanhydride (48.1 mg, 0.199 mmol) in CCl4 (10 mL), and the resulting mixture was stirred at 70° C. for 18 h. The reaction was stopped. The mixture was concentrated under reduced pressure, separated between water and EtOAc. The organic extract was dried and concentrated under reduced pressure to give the title compound, which was used in the next step without further purification. [M+H] calc'd for C25H31BrN5O4, 603. found, 604.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customseparated between water and EtOAc
  3. extractionThe organic extract
  4. customwas dried
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f8852ce12d7440cfb413694882d588b6
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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