Water → 2-[[(1R,2S)-2-aminocyclohexyl]amino]-4-(3-fluoro-4-imidazol-1-ylanilino)pyrimidine-5-carboxamide

HRID 1846705Notes

Reaction equation

HRID 1846705 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@@H:3]1[NH:8][C:9](=O)OC(C)(C)C.N1(OC2[N:31]=[C:30]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([N:39]4[CH:43]=[CH:42][N:41]=[CH:40]4)=[C:35]([F:44])[CH:34]=3)[C:29]([C:45]([NH2:47])=[O:46])=[CH:28][N:27]=2)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.O>CN1C(=O)CCC1.CCOC(C)=O>[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH:8][C:9]1[N:31]=[C:30]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([N:39]3[CH:43]=[CH:42][N:41]=[CH:40]3)=[C:35]([F:44])[CH:34]=2)[C:29]([C:45]([NH2:47])=[O:46])=[CH:28][N:27]=1

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 574718872-(1H-benzo[d][1,2,3]triazol-1-yloxy)-4-(3-fluoro-4-(1H-imidazol-1-yl)phenylamino)pyrimidine-5-carboxamide

Product 1

HCID 574718842-[[(1R,2S)-2-aminocyclohexyl]amino]-4-(3-fluoro-4-imidazol-1-ylanilino)pyrimidine-5-carboxamideYield 43.1%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (0.30 M in NMP, 1.00 mL, 0.300 mmol) in NMP (1 mL) was added to 2-(1H-benzo[d][1,2,3]triazol-1-yloxy)-4-(3-fluoro-4-(1H-imidazol-1-yl)phenylamino)pyrimidine-5-carboxamide (57 mg, 0.13 mmol). DIEA (0.100 mL, 0.57 mmol) was also added. The mixture was stirred at 90 C for 1 h. After being cooled to room temperature, water and EtOAc were added. The organic phase was separated, washed with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo. The residue was dissolved in CH2Cl2 (1 mL) and TFA (1 mL). The solution was stirred at room temperature for 60 min. It was concentrated in vacuo. The residue was purified by HPLC to give the titled compound (23 mg). MS 411.3 (M+H). UV λ=247.8, 299.8 nm.

Workup

  1. customThe organic phase was separated
  2. washwashed with 5% NaHCO3
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. dissolutionThe residue was dissolved in CH2Cl2 (1 mL)
  6. stirringThe solution was stirred at room temperature for 60 min
  7. concentrationIt was concentrated in vacuo
  8. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-112ed30da66d4a108d6821dcc2abfac6
Source dataset
uspto-grants-2015_02
Patent number
US08952027B2

Reaction notes

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