Water → Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(m-tolylamino)nicotinate

HRID 515975ノート

反応式

HRID 515975 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:16]=[C:17]([CH3:21])[CH:18]=[CH:19][CH:20]=2)[N:3]=1.[NH2:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]1[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].CCN(CC)CC.O>CCOC(C)=O>[C:32]([O:31][C:30]([NH:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@H:23]1[NH:22][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)=[O:36])([CH3:35])([CH3:33])[CH3:34]

参加物

6

反応物 4

HCID 962WaterHCID 8471TriethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 58317587Methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinate

生成物 1

HCID 67238782Methyl 6-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-cyano-2-(m-tolylamino)nicotinate収率 79.5%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

A solution of methyl 6-chloro-4-cyano-2-(m-tolylamino)nicotinate (198 mg, 0.656 mmol), tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (562 mg, 2.62 mmol) and Et3N (0.402 mL, 2.89 mmol) was stirred at reflux overnight. To the resulting mixture were added H2O and EtOAc. The aqueous phase was extracted with EtOAc. The organic layers were combined, washed with brine, dried over MgSO4, and evaporated. The residue was triturated with EtOAc. The resulting solid was filtered, rinsed with EtOAc, and dried to give the title compound as a yellow solid (250 mg, 79%). 1H NMR (500 MHz, CDCl3) δ ppm 1.23-1.77 (m, 17 H), 2.34 (s, 3 H), 3.94 (br s, 3 H), 3.98 (br s, 1H), 4.80 (s, 1H), 6.15 (s, 1 H), 6.91 (d, J=5.37 Hz, 1 H), 7.21 (t, J=7.81 Hz, 1H), 7.29 (s, 1H), 7.47-7.55 (m, 1 H), 10.64 (br s, 1 H).

後処理

  1. temperatureat reflux overnight
  2. extractionThe aqueous phase was extracted with EtOAc
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe residue was triturated with EtOAc
  7. filtrationThe resulting solid was filtered
  8. washrinsed with EtOAc
  9. customdried

出典と根拠

ORDレコード
ord-3f6dc78555f64dc792494ed07efcb36e
出典データセット
uspto-grants-2015_08
特許番号
US09108970B2

反応ノート

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