tert-Butanol → Tert-butyl 3-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoate

HRID 886996노트

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HRID 886996 반응식
C(O)(C)(C)C.CCN(C(C)C)C(C)C.Cl[C:16]1[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]2[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=2)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[N:17]=1.C(O)(=O)C.[NH2:44][CH2:45][C:46]1[C:47]([N:52]([CH3:57])[S:53]([CH3:56])(=[O:55])=[O:54])=[N:48][CH:49]=[CH:50][CH:51]=1>ClCCCl>[CH3:57][N:52]([S:53]([CH3:56])(=[O:55])=[O:54])[C:47]1[C:46]([CH2:45][NH:44][C:16]2[C:21]([C:22]([F:25])([F:24])[F:23])=[CH:20][N:19]=[C:18]([NH:26][C:27]3[CH:28]=[C:29]([CH:37]=[CH:38][CH:39]=3)[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[N:17]=2)=[CH:51][CH:50]=[CH:49][N:48]=1

참가 물질

6

반응물 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 57584682Tert-butyl 3-({4-chloro-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoateHCID 67099950N-(3-(Aminomethyl)pyridin-2-yl)-N-methylmethanesulfonamide acetate

생성물 1

HCID 25116907Tert-butyl 3-({4-[({2-[methyl(methylsulfonyl)amino]pyridin-3-yl}methyl)amino]-5-(trifluoromethyl)pyrimidin-2-yl}amino)benzoate

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

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온도
80 °C

실험 절차

A solution of tert-butanol (20.0 mL), DCE (20.0 mL) and DIEA (3.13 mL, 18.0 mmol) was treated with C8 (5.60 g, 15.0 mmol) and B5 (5.02 g, 15.0 mmol), and the resulting mixture was stirred at 80° C. under an atmosphere of nitrogen for 16 hours. The mixture was cooled to 25° C. and concentrated. The resultant residue was partitioned between EtOAc and 1 N sodium hydroxide, and the organic phase was collected. The aqueous layer was extracted with EtOAc, and the combined organic phases were dried over MgSO4 and filtered. The resultant filtrate was concentrated under reduced pressure, and the resultant residue was triturated with hot EtOAc to provide 9 as a white solid. Yield: 7.83 grams, 95%. LC/MS (standard) 25°=3.0 min., m/z 553.6 (MH+). HPLC (FAK1) 25°=8.14 min. 1H NMR (d6-DMSO) δ: 9.75 (bs, 1H), 8.44 (d, J=5.2 Hz., 1H), 8.29 (s, 1H), 8.05 (bs, 1H), 7.82 (d, J=7.8 Hz., 1H), 7.60 (t, J=5.7 Hz., 1H), 7.44-7.40 (m, 2H), 7.17 (t, J=5.7 Hz, 1H), 4.82 (d, J=5.7 Hz., 2H), 3.16 (s, 3H), 3.13 (s, 3H), 1.51 (s, 9H) ppm. FAK IC50: 0.0006 μM

후처리

  1. temperatureThe mixture was cooled to 25° C.
  2. concentrationconcentrated
  3. customThe resultant residue was partitioned between EtOAc and 1 N sodium hydroxide
  4. customthe organic phase was collected
  5. extractionThe aqueous layer was extracted with EtOAc
  6. dry with materialthe combined organic phases were dried over MgSO4
  7. filtrationfiltered
  8. concentrationThe resultant filtrate was concentrated under reduced pressure
  9. customthe resultant residue was triturated with hot EtOAc

출처 및 근거

ORD 기록
ord-c7d1049a3f3345a3bcc62bb6128df397
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08247411B2

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