Water → Methyl 2-(1H-indazol-6-ylamino)-6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyanonicotinate

HRID 711448

Reaction equation

HRID 711448 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:10][C:11]3[N:20]=[C:19](Cl)[CH:18]=[C:17]([C:22]#[N:23])[C:12]=3[C:13]([O:15][CH3:16])=[O:14])[CH:8]=2)[CH:3]=[N:2]1.[NH2:24][C@@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]1[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35].CCN(CC)CC.O>C1COCC1.CCOC(C)=O>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([NH:10][C:11]3[N:20]=[C:19]([NH:24][C@@H:25]4[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]4[NH:31][C:32]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:38])[CH:18]=[C:17]([C:22]#[N:23])[C:12]=3[C:13]([O:15][CH3:16])=[O:14])[CH:8]=2)[CH:3]=[N:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 58317650Methyl 2-(1H-indazol-6-ylamino)-6-chloro-4-cyanonicotinate

Product 1

HCID 67238712Methyl 2-(1H-indazol-6-ylamino)-6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyanonicotinateYield 62%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 2-(1H-indazol-6-ylamino)-6-chloro-4-cyanonicotinate (115 mg, 0.351 mmol), tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (90 mg, 0.421 mmol) and Et3N (0.073 mL, 0.526 mmol) in THF (1 mL) was stirred at reflux overnight. Water and EtOAc were added to the mixture. The aqueous phase was extracted with EtOAc. The organic phases were combined, washed with H2O and brine, dried over MgSO4, and evaporated. The residue was rinsed with EtOAc to give the title compound as yellow solid (110 mg, 62.0%). 1H NMR (500 MHz, CDCl3) δ ppm 1.00-1.86 (m, 17H), 3.84 (s, 3H), 3.91 (br s, 1H), 4.12 (br s, 1H), 6.51 (s, 1H), 6.63 (d, J=8.79 Hz, 1H), 7.13 (d, J=8.30 Hz, 1H), 7.97 (s, 1H), 8.03 (br s, 1H), 10.71 (br s, 1H), 12.87 (br s, 1H).

Workup

  1. temperatureat reflux overnight
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washwashed with H2O and brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. washThe residue was rinsed with EtOAc

Sources & evidence

ORD record
ord-3c0a00146f804a8c9b20b034629d470f
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Linked notes

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