(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamide → {4-[4-(5-Bromo-pyridin-2-ylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenylsulfanyl]-phenyl}-carbamic acid 2,2,2-trichloro-ethyl ester

HRID 605326노트

반응식

HRID 605326 반응식
[Cl:1][C:2]([Cl:33])([Cl:32])[CH2:3][O:4][C:5](=[O:31])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][N:23]=3)=[CH:16][C:15]=2[NH2:30])=[CH:9][CH:8]=1.C([C:36]1[C:37]([N:45]=[CH:46][N:47]([CH3:49])C)=[N:38][C:39]([CH:42]([CH3:44])[CH3:43])=[CH:40][CH:41]=1)#N>C(O)(=O)C>[Cl:33][C:2]([Cl:1])([Cl:32])[CH2:3][O:4][C:5](=[O:31])[NH:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][C:14]2[CH:19]=[CH:18][C:17]([C:20](=[O:29])[NH:21][C:22]3[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][N:23]=3)=[CH:16][C:15]=2[NH:30][C:49]2[C:36]3[CH:41]=[CH:40][C:39]([CH:42]([CH3:43])[CH3:44])=[N:38][C:37]=3[N:45]=[CH:46][N:47]=2)=[CH:9][CH:8]=1

참가 물질

4

반응물 2

HCID 66808369(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamideHCID 67040870{4-[2-Amino-4-(5-bromo-pyridin-2-ylcarbamoyl)-phenylsulfanyl]-phenyl}-carbamic acid 2,2,2-trichloro-ethyl ester

생성물 1

HCID 67040673{4-[4-(5-Bromo-pyridin-2-ylcarbamoyl)-2-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-phenylsulfanyl]-phenyl}-carbamic acid 2,2,2-trichloro-ethyl ester수율 79%

시약·촉매·용매 1

HCID 176Acetic Acid용매

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온도
140 °C

실험 절차

A mixture of the products of Example 364D (3.05 g, 5.16 mmol) and Example 8E (N′-(3-cyano-6-isopropyl-pyridin-2-yl)-N,N-dimethyl-formamidine) (1.34 g, 6.20 mmol, 1.2 equiv.) in 25 mL of glacial acetic acid was heated in a 140° C. preheated oil bath for 45 minutes. The reaction mixture was cooled, evaporated in vacuo and the residue partitioned between ethyl acetate (250 mL) and water (100 mL). The organic phase was then washed with saturated aqueous sodium bicarbonate and then brine, dried over anhydrous magnesium sulfate, filtered, and evaporated under reduced pressure. The resulting residue was triturated with methanol, filtered, and dried in vacuo to provide the title compound (3.10 g, 79%) as a beige solid. MS (ESI+) m/z 762/764 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.33 (d, J=6.99 Hz, 6 H), 3.16-3.26 (m, 1 H), 4.97 (s, 2 H), 6.96 (s, 1 H), 7.43 (d, J=8.82 Hz, 2 H), 7.59 (s, 2 H), 7.86 (s, 1 H), 8.01-8.10 (m, 3 H), 8.15-8.20 (m, 1 H), 8.50 (d, J=2.57 Hz, 1 H), 8.57 (s, 1 H), 8.84 (s, 1 H), 10.23 (s, 1 H), 10.40 (s, 1 H), 10.94 (s, 1 H).

후처리

  1. customfor 45 minutes
  2. temperatureThe reaction mixture was cooled
  3. customevaporated in vacuo
  4. customthe residue partitioned between ethyl acetate (250 mL) and water (100 mL)
  5. washThe organic phase was then washed with saturated aqueous sodium bicarbonate
  6. dry with materialbrine, dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe resulting residue was triturated with methanol
  10. filtrationfiltered
  11. customdried in vacuo

출처 및 근거

ORD 기록
ord-d789f955417046719fd50d5a02111539
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07910595B2

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