Diisopropylethylamine → Methyl 6-(cis-2-Amino-3,3-difluorocyclohexylamino)-4-cyano-2-(m-tolylamino)nicotinate

HRID 711547Notes

Reaction equation

HRID 711547 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.Cl.[F:23][C:24]1([F:32])[CH2:29][CH2:28][CH2:27][C@@H:26]([NH2:30])[C@H:25]1[NH2:31].CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[NH2:31][C@H:25]1[C:24]([F:32])([F:23])[CH2:29][CH2:28][CH2:27][C@H:26]1[NH:30][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

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 58317587Methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinateHCID 67238749cis-3,3-Difluorocyclohexane-1,2-diamine hydrochloride

Product 1

HCID 67237563Methyl 6-(cis-2-Amino-3,3-difluorocyclohexylamino)-4-cyano-2-(m-tolylamino)nicotinate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a screw-cap vial was added methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinate (200 mg, 0.663 mmol), cis-3,3-difluorocyclohexane-1,2-diamine hydrochloride (148 mg, 0.795 mmol), and DIPEA (347 μL, 1.989 mmol) in DMF (3.9 mL). The resulting brownish-yellow mixture was stirred at RT for 2 h and then at 60° C. for 12 h. The reaction mixture was cooled to RT, diluted with EtOAc (30 mL) and washed with water (2×10 mL) and brine (20 mL). The organic layer was collected, dried over Na2SO4, and concentrated to give a thick brown oil, which included the title compound and isomers (328 mg, 119%). The crude product was used without further purification. [M+H] calc'd for C21H23F2N5O2, 416. found, 416.

Workup

  1. waitat 60° C. for 12 h
  2. temperatureThe reaction mixture was cooled to RT
  3. washwashed with water (2×10 mL) and brine (20 mL)
  4. customThe organic layer was collected
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give a thick brown oil, which

Sources & evidence

ORD record
ord-491419c863fb46cf9f8d883ff82a7611
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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