Water → HCID 44243179, 화합물

HRID 1917685노트

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HRID 1917685 반응식
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]3[C:30]4[C:25](=[CH:26][C:27]([O:35][CH3:36])=[C:28]([O:31][CH2:32][CH2:33]Cl)[CH:29]=4)[N:24]=[CH:23][N:22]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.CCN(C(C)C)C(C)C.O>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C=O)C>[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]3[C:30]4[C:25](=[CH:26][C:27]([O:35][CH3:36])=[C:28]([O:31][CH2:32][CH2:33][N:37]5[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]5)[CH:29]=4)[N:24]=[CH:23][N:22]=3)[CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 962WaterHCID 8082PiperidineHCID 81531DiisopropylethylamineHCID 668763401-(5-Tert-butylisoxazol-3-yl)-3-(3-(6-(2-chloroethoxy)-7-methoxyquinazolin-4-yloxy)phenyl)urea

생성물 1

HCID 44243179HCID 44243179, 화합물수율 13.3%

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

1-(5-tert-butylisoxazol-3-yl)-3-(3-(6-(2-chloroethoxy)-7-methoxyquinazolin-4-yloxy)phenyl)urea (200 mg, 0.39 mmol) from the previous step was treated with piperidine (0.116 mL, 1.17 mmol), tetrabutylammonium iodide (0.39 mmol) and N,N′-diisopropylethylamine (0.78 mmol) in N,N′-dimethylformamide. The mixture was heated to 60° C. for 56 h and cooled to room temperature. Water was added and the solid filtered off and dried. The crude solid was purified by preparative HPLC (phenylhexyl reverse phase column) and the obtained solid triturated with water (10 mL) and drops of methanol, then filtered off and dried under high vacuum to afford 1-(5-tert-butylisoxazol-3-yl)-3-(3-(7-methoxy-6-(2-(piperidin-1-yl)ethoxy)quinazolin-4-yloxy)phenyl)urea as a colorless solid (29 mg, 13%). 1H NMR (300 MHz, DMSO-d6) δ 9.80 (brs, 1H), 9.10 (brs, 1H), 8.55 (s, 1H), 7.64 (s, 1H), 7.59 (s, 1H), 7.37-7.42 (m, 2H), 7.26 (m, 1H), 6.96 (m, 1H), 6.48 (s, 1H), 4.26-4.30 (m, 2H), 3.99 (s, 3H), 2.72-2.76 (m, 2H), 2.40-2.50 (m, 4H), 1.48-1.52 (m, 4H), 1.37-1.39 (m, 2H), 1.30 (s, 9H); LC-MS (ESI) m/z 561 (M+H)+.

후처리

  1. temperaturecooled to room temperature
  2. filtrationthe solid filtered off
  3. customdried
  4. customThe crude solid was purified by preparative HPLC (phenylhexyl reverse phase column)
  5. customthe obtained solid triturated with water (10 mL)
  6. filtrationfiltered off
  7. customdried under high vacuum

출처 및 근거

ORD 기록
ord-38d0088fd6f0404c800a799ce9303e33
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08618289B2

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