Water → Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinate

HRID 515987

반응식

HRID 515987 반응식
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:20]=[CH:19][C:18]([F:21])=[C:17]([CH3:22])[CH:16]=2)[N:3]=1.CCN(CC)CC.[NH2:30][C@@H:31]1[CH2:36][CH2:35][CH2:34][CH2:33][C@@H:32]1[NH:37][C:38](=[O:44])[O:39][C:40]([CH3:43])([CH3:42])[CH3:41].O>C1COCC1.CCOC(C)=O>[C:40]([O:39][C:38]([NH:37][C@H:32]1[CH2:33][CH2:34][CH2:35][CH2:36][C@H:31]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:20]=[CH:19][C:18]([F:21])=[C:17]([CH3:22])[CH:16]=2)[N:3]=1)=[O:44])([CH3:43])([CH3:41])[CH3:42]

참가 물질

7

반응물 4

HCID 962WaterHCID 8471TriethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 58317541Methyl 6-chloro-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinate

생성물 1

HCID 67237937Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinate수율 12.4%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

반응 조건

온도
80 °C

실험 절차

A mixture of methyl 6-chloro-4-cyano-2-(4-fluoro-3-methylphenylamino)nicotinate (390 mg, 1.220 mmol), Et3N (0.204 mL, 1.464 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (392 mg, 1.830 mmol) in THF (5 mL) was stirred at 80° C. overnight. Water and EtOAc were subsequently added to the mixture and 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 diluted with EtOAc and filtered to give the title compound as a yellow solid (75 mg, 12.36%). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.03-1.71 (m, 17 H), 2.22 (d, J=0.98 Hz, 3 H), 3.80-3.82 (m, 3 H), 3.83 (br s, 1 H), 4.01-4.09 (m, 1 H), 6.48 (s, 1 H), 6.62 (d, J=7.81 Hz, 1 H), 7.06 (t, J=9.03, 1 H), 7.39 (d, J=4.39 Hz, 1 H), 7.50-7.68 (m, 1 H), 10.41 (br s, 1 H).

후처리

  1. extractionthe aqueous phase was extracted with EtOAc
  2. washwashed with H2O and brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. additionThe residue was diluted with EtOAc
  6. filtrationfiltered

출처 및 근거

ORD 기록
ord-6e2b9f40e73343228fe8625baa4a1eb3
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108970B2

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