Triethylamine → Ethyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylate

HRID 515961

반응식

HRID 515961 반응식
Cl[C:2]1[N:7]=[C:6]([CH2:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])[C:5]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:4]([NH:25][C:26]2[CH:27]=[C:28]([CH3:32])[CH:29]=[CH:30][CH:31]=2)[N:3]=1.[NH2:33][C@@H:34]1[CH2:39][CH2:38][CH2:37][CH2:36][C@@H:35]1[NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44].CCN(CC)CC.C([O-])(O)=O.[Na+]>CC(N(C)C)=O>[C:43]([O:42][C:41]([NH:40][C@H:35]1[CH2:36][CH2:37][CH2:38][CH2:39][C@H:34]1[NH:33][C:2]1[N:7]=[C:6]([CH2:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])[C:5]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[C:4]([NH:25][C:26]2[CH:27]=[C:28]([CH3:32])[CH:29]=[CH:30][CH:31]=2)[N:3]=1)=[O:47])([CH3:46])([CH3:44])[CH3:45]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 58317687Ethyl 2-chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylate

생성물 1

HCID 58317681Ethyl 2-((1R,2S)-2-(tert-butoxycarbonylamino)cyclohexylamino)-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylate수율 92%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
80 °C

실험 절차

A mixture of ethyl 2-chloro-4-((1,3-dioxoisoindolin-2-yl)methyl)-6-(m-tolylamino)pyrimidine-5-carboxylate (96.3 mg, 0.214 mmol), tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (58.14 mg, 0.271 mmol) and Et3N (0.030 mL, 0.214 mmol) in DMA (2 mL) was stirred at 80° C. for 3 h. Saturated aq NaHCO3 was added to the mixture, which was extracted with EtOAc. The combined organic layers were washed with aqueous NaHCO3, water, and brine, were dried over anhydrous Na2SO4, and then filtered through SiO2. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (SiO2, hexanes/EtOAc=3/1) to give the title compound as a yellow oil (123.8 mg, 92%). 1H NMR (400 MHz, CDCl3) δ ppm 1.12-1.71 (m, 20H), 2.33 (s, 3H), 3.39-3.57 (m, 1H), 3.84-3.99 (m, 1H), 4.42 (q, J=7.2 Hz, 2H), 4.55-4.79 (m, 1H), 5.16 (s, 2H), 5.41 (br s, 1H), 6.87-6.89 (m, 1H), 7.16-7.49 (m, 3H), 7.74-7.75 (m, 2H), 7.90-7.91 (m, 2H), 10.68-10.81 (m, 1H). [M+H] calc'd for C34H41N6O6, 629; found, 629.

후처리

  1. extractionwas extracted with EtOAc
  2. washThe combined organic layers were washed with aqueous NaHCO3, water, and brine
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered through SiO2
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by column chromatography (SiO2, hexanes/EtOAc=3/1)

출처 및 근거

ORD 기록
ord-ca628fc62b7d4378891510dbcf80d5b6
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108970B2

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