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

HRID 515987

反応式

HRID 515987 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-6e2b9f40e73343228fe8625baa4a1eb3
出典データセット
uspto-grants-2015_08
特許番号
US09108970B2

関連ノート

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