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

HRID 711440
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HRID 711440 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: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]
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참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

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, 17H), 2.34 (s, 3H), 3.94 (br s, 3H), 3.98 (br s, 1H), 4.80 (s, 1H), 6.15 (s, 1H), 6.91 (d, J=5.37 Hz, 1H), 7.21 (t, J=7.81 Hz, 1H), 7.29 (s, 1H), 7.47-7.55 (m, 1H), 10.64 (br s, 1H).

후처리

  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

출처 및 근거

ORD 기록
ord-efeac7de92ed4186bd99bd22cad6f278
출처 데이터셋
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09181255B2

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