Ethyl Acetate → HCID 66990901, compound

HRID 2367242Notes

Reaction equation

HRID 2367242 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]3[C@H:22]([C:23]([F:26])([F:25])[F:24])[CH2:21][CH2:20][C@H:19]([C:27]([NH:29][CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)=O)[CH2:18]3)[CH:10]=2)=[CH:5][C:4]=1F)#[N:2].[OH2:37].[NH2:38][NH2:39].CCOC(C)=O>C(O)C>[NH2:2][C:1]1[C:3]2[C:4](=[CH:5][C:6]([C:9]3[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]4[C@H:22]([C:23]([F:26])([F:25])[F:24])[CH2:21][CH2:20][C@H:19]([C:27]([NH:29][CH:30]5[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]5)=[O:37])[CH2:18]4)[CH:10]=3)=[CH:7][CH:8]=2)[NH:39][N:38]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24654Hydrazine hydrate (1:1)HCID 66990661HCID 66990661, compound

Product 1

HCID 66990901HCID 66990901, compoundYield 74.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To cis-1-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-cyclohexyl-6-(trifluoromethyl)-3-piperidinecarboxamide (152 mg, 0.301 mmol) in ethanol (6 mL) was added hydrazine monohydrate (0.4 mL, 8.16 mmol), and the reaction mixture was stirred overnight at 100° C. into a sealed tube. The reaction was allowed to cool to room temperature and poured onto water and EtOAc. The organic layer was separated, and the aqueous layer was further extracted with EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated. Flash chromatography on SiO2 (gradient: 100% CH2Cl2 to 90:10:1 CH2Cl2:CH3OH:NH4OH) afforded the title compound (116 mg) as an off-white solid. LC-MS (ES) m/z=517 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.05-1.34 (m, 5H), 1.56 (m, 1H), 1.62-1.85 (m, 7H), 2.08. (m, 1H), 2.34 (m, 1H), 2.84 (s, 3H), 3.07 (bs, 1H), 3.53 (m, 1H), 5.39 (s, 2H), 6.73 (bs, 1H), 6.78 (s, 1H), 7.63-7.69 (m, 1H), 7.70-7.75 (m, 1H), 7.84 (d, J=7.8 Hz, 1H), 8.02 (bs, 1H), 11.52 (s, 1H).

Workup

  1. temperatureto cool to room temperature
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was further extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-9670a14a1c2346ec99233b211872440d
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…