Methanol → 2-(5-{2-[3-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureidomethyl]-4-fluorophenoxy}-indazol-1-yl)-N,N-dimethylacetamide

HRID 909224노트

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HRID 909224 반응식
[NH2:1][CH2:2][C:3]1[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:4]=1[O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][C:16]([N:18]([CH3:20])[CH3:19])=[O:17])[N:10]=[CH:9]2.ClC(Cl)(Cl)C[O:29][C:30](=O)[NH:31][C:32]1[N:33]([C:41]2[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=2)[N:34]=[C:35]([C:37]([CH3:40])([CH3:39])[CH3:38])[CH:36]=1.CCN(C(C)C)C(C)C.CO>CN(C=O)C.ClCCl>[C:37]([C:35]1[CH:36]=[C:32]([NH:31][C:30](=[O:29])[NH:1][CH2:2][C:3]2[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:4]=2[O:5][C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[N:11]([CH2:15][C:16]([N:18]([CH3:20])[CH3:19])=[O:17])[N:10]=[CH:9]3)[N:33]([C:41]2[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=2)[N:34]=1)([CH3:40])([CH3:38])[CH3:39]

참가 물질

7

반응물 4

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 99310942,2,2-Trichloroethyl 3-tert-butyl-1-P-tolyl-1H-pyrazol-5-ylcarbamateHCID 674102372-[5-(2-Aminomethyl-4-fluorophenoxy)-indazol-1-yl]-N,N-dimethylacetamide

생성물 1

HCID 426422102-(5-{2-[3-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-ureidomethyl]-4-fluorophenoxy}-indazol-1-yl)-N,N-dimethylacetamide수율 36.3%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
80 °C

실험 절차

To a solution of 2-[5-(2-aminomethyl-4-fluoro-phenoxy)-indazol-1-yl]-N,N-dimethylacetamide (46d) (0.010 g, 0.029 mmol) and (5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-carbamic acid 2,2,2-trichloroethyl ester (0.013 g, 0.032 mmol) in DMF (1 mL) was added DIEA (0.01 mL, 0.058 mmol). The mixture was heated to 80° C. for 18 hours under N2 atmosphere. The mixture was concentrated under reduced pressure and dissolved in dichloromethane. The solution was washed with 1N HCl, filtered, and concentrated under reduced pressure. The oil was chromatographed eluting with dichloromethane/ether (10:1) and then 5% MeOH in dichloromethane to afford 6.3 mg of pale yellow oil (36% yield). MS (APCI+) m/z 598 (M+1) detected; 1H NMR (400 mHz, DMSO-D6) δ 8.29 (s, 1H), 7.97 (s, 1H), 7.58 (d, 1H), 7.36 (d, 2H), 7.28 (d, 2H), 7.19 (d, 1H), 7.12 (d, 1H), 7.07 (m, 2H), 6.99 (m, 1H), 6.84 (m, 1H), 6.24 (s, 1H), 5.40 (s, 2H), 4.28 (d, 2H), 3.10 (s, 3H), 2.84 (s, 3H), 2.35 (s, 3H), 1.25 (s, 9H).

후처리

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutiondissolved in dichloromethane
  3. washThe solution was washed with 1N HCl
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe oil was chromatographed
  7. washeluting with dichloromethane/ether (10:1)

출처 및 근거

ORD 기록
ord-4ece8d93b7364c4fb61af34da13f0428
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08017641B2

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