Water → Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(m-tolylamino)nicotinate

HRID 515975Notes

Reaction equation

HRID 515975 reaction equation
Cl[C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=2)[N:3]=1.[NH2:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].CCN(CC)CC.O>CCOC(C)=O>[C:32]([O:31][C:30]([NH:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@H:23]1[NH:22][C:2]1[CH:11]=[C:10]([C:12]#[N:13])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([NH:14][C:15]2[CH:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=2)[N:3]=1)=[O:36])([CH3:35])([CH3:33])[CH3:34]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 58317587Methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinate

Product 1

HCID 67238782Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(m-tolylamino)nicotinateYield 79.5%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinate (198 mg, 0.656 mmol), tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (562 mg, 2.62 mmol) and Et3N (0.402 mL, 2.89 mmol) was stirred at reflux overnight. To the resulting mixture were added H2O and EtOAc. The aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over MgSO4, and evaporated. The residue was triturated with EtOAc. The resulting solid was filtered, rinsed with EtOAc, and dried to give the title compound as a yellow solid (250 mg, 79%). 1H NMR (500 MHz, CDCl3) δ ppm 1.23-1.77 (m, 17 H), 2.34 (s, 3 H), 3.94 (br s, 3 H), 3.98 (br s, 1H), 4.80 (s, 1H), 6.15 (s, 1 H), 6.91 (d, J=5.37 Hz, 1 H), 7.21 (t, J=7.81 Hz, 1H), 7.29 (s, 1H), 7.47-7.55 (m, 1 H), 10.64 (br s, 1 H).

Workup

  1. temperatureat reflux overnight
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe residue was triturated with EtOAc
  7. filtrationThe resulting solid was filtered
  8. washrinsed with EtOAc
  9. customdried

Sources & evidence

ORD record
ord-3f6dc78555f64dc792494ed07efcb36e
Source dataset
uspto-grants-2015_08
Patent number
US09108970B2

Reaction notes

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