Piperidine → N-[(1R,6S)-6-Amino-2,2-difluorocyclohexyl]-5-(difluoromethyl)-4-(imidazo[1,2-b]pyridazin-3-yl)thiophene-2-carboxamide

HRID 2046417Notes

Reaction equation

HRID 2046417 reaction equation
C1C2C(COC(=O)[NH:17][C@H:18]3[CH2:23][CH2:22][CH2:21][C:20]([F:25])([F:24])[C@@H:19]3[NH:26][C:27]([C:29]3[S:30][C:31]([CH:43]([F:45])[F:44])=[C:32]([C:34]4[N:38]5[N:39]=[CH:40][CH:41]=[CH:42][C:37]5=[N:36][CH:35]=4)[CH:33]=3)=[O:28])C3C(=CC=CC=3)C=2C=CC=1.N1CCCCC1>CN(C=O)C.O>[NH2:17][C@@H:18]1[C@@H:19]([NH:26][C:27]([C:29]2[S:30][C:31]([CH:43]([F:44])[F:45])=[C:32]([C:34]3[N:38]4[N:39]=[CH:40][CH:41]=[CH:42][C:37]4=[N:36][CH:35]=3)[CH:33]=2)=[O:28])[C:20]([F:24])([F:25])[CH2:21][CH2:22][CH2:23]1

Participants

5

Reactant 2

HCID 8082PiperidineHCID 671453369H-fluoren-9-ylmethyl[(1S,2R)-2-({[5-(difluoromethyl)-4-(imidazo[1,2-b]pyridazin-3-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate

Product 1

HCID 67123107N-[(1R,6S)-6-Amino-2,2-difluorocyclohexyl]-5-(difluoromethyl)-4-(imidazo[1,2-b]pyridazin-3-yl)thiophene-2-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 9H-fluoren-9-ylmethyl[(1S,2R)-2-({[5-(difluoromethyl)-4-(imidazo[1,2-b]pyridazin-3-yl)thiophen-2-yl]carbonyl}amino)-3,3-difluorocyclohexyl]carbamate (27 mg, 0.042 mmol) in DMF (0.8 mL) was added piperidine (0.08 mL, 0.83 mmol). The mixture was left to stir for 1 h, diluted with water, and extracted with EtOAc. The organic layer was dried, concentrated, and purified by flash chromatography to afford the title compound. 1H NMR (500 MHz, CD3SOCD3) δ 8.38 (s, 1H); 8.72 (d, 1H); 8.68 (dd, 1H); 8.43 (s, 1H); 8.27 (dd, 1H); 7.97 (s, 1H); 7.38 (dd, 1H); 7.35 (t, 1H); 4.05 (m, 1H); 2.82 (m, 1H); 1.30-2.10 (m, 6H). LRMS (APCI) calc'd for (C18H18F4N5OS) [M+H]+, 428.1. found 428.1.

Workup

  1. waitThe mixture was left
  2. extractionextracted with EtOAc
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. custompurified by flash chromatography

Sources & evidence

ORD record
ord-bb60dd5fb01e43c59a49aaca295c07b9
Source dataset
uspto-grants-2013_11
Patent number
US08592425B2

Reaction notes

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