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Tetrahydrofuran → 4-(3-tert-Butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)phenyl]ureido}pyrazol-1-yl)-2-methyl-N-(2-morpholin-4-yl-ethyl)benzene-sulfonamide

HRID 1174882
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HRID 1174882 반응식
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][CH2:17][CH2:18][N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)(=[O:15])=[O:14])=[C:9]([CH3:25])[CH:8]=2)[N:5]=[C:4]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:3]=1.[F:30][C:31]1[CH:36]=[C:35]([O:37][C:38]2[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[CH:39]=2)[CH:34]=[CH:33][C:32]=1[NH2:45].C1C[O:49][CH2:48]C1>ClCCCl>[C:26]([C:4]1[CH:3]=[C:2]([NH:1][C:48]([NH:45][C:32]2[CH:33]=[CH:34][C:35]([O:37][C:38]3[CH:43]=[CH:42][N:41]=[C:40]([CH3:44])[CH:39]=3)=[CH:36][C:31]=2[F:30])=[O:49])[N:6]([C:7]2[CH:12]=[CH:11][C:10]([S:13]([NH:16][CH2:17][CH2:18][N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)(=[O:15])=[O:14])=[C:9]([CH3:25])[CH:8]=2)[N:5]=1)([CH3:29])([CH3:28])[CH3:27]
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참가 물질

5

반응물 3

HCID 8028TetrahydrofuranHCID 536301804-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-methyl-N-(2-morpholin-4-yl-ethyl)benzenesulfonamideHCID 595579602-Fluoro-4-(2-methylpyridin-4-yloxy)phenylamine

생성물 1

HCID 115783564-(3-tert-Butyl-5-{3-[2-fluoro-4-(2-methyl-pyridin-4-yloxy)phenyl]ureido}pyrazol-1-yl)-2-methyl-N-(2-morpholin-4-yl-ethyl)benzene-sulfonamide수율 23%

시약·촉매·용매 1

HCID 11
1,2-Dichloroethane
용매

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온도
50 °C

실험 절차

To a solution of 4-(5-amino-3-tert-butyl-pyrazol-1-yl)-2-methyl-N-(2-morpholin-4-yl-ethyl)benzenesulfonamide (150 mg, 0.36 mmol) in anhydrous DCE (1 mL) was added CDT (64 mg, 0.39 mmol, 1.1 eq), and the reaction was stirred under nitrogen at 50° C. for 18 h. A solution of 2-fluoro-4-(2-methyl-pyridin-4-yloxy)phenylamine (86 mg, 0.39 mmol, 1.1 eq) in anhydrous THF (1 mL) was added to the reaction, and the solution was stirred under at 50° C. for 3 days. The reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL). The organic layer was washed with brine, dried over Na2SO4, and concentrated at reduced pressure. The crude product was purified by HPLC and recrystallized from DCM/hexane to give 55 mg (23%) of the title compound as a white solid. 1H-NMR (DMSO-d6) δ 8.92 (d, J=14.4 Hz, 2H), 8.30 (d, J=5.7 Hz, 1H), 8.07 (t, J=9 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.68 (t, J=6 Hz, 1H), 7.58 to 7.51 (m, 2H), 7.25 (dd, J=11.4, 2.4 Hz, 1H), 6.97 to 6.92 (m, 1H), 6.77 (d, J=2.4 Hz, 1H), 6.74 to 6.70 (m, 1H), 6.41 (s, 1H), 3.45 (t, J=4.5 Hz, 4H), 2.93 (q, J=6H, 2H), 2.65 (s, 3H), 2.39 (s, 3H), 2.25 (t, J=6.9 Hz, 2H), 2.20 to 2.17 (m, 4H), 1.27 (s, 9H); MS LC-MS [M+H]+=666, RT=2.26 min.

후처리

  1. stirringthe solution was stirred under at 50° C. for 3 days
  2. customThe reaction mixture was partitioned between EtOAc (50 mL) and water (50 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated at reduced pressure
  6. customThe crude product was purified by HPLC
  7. customrecrystallized from DCM/hexane

출처 및 근거

ORD 기록
ord-12045130b93745c98ca8a839684cf5d2
출처 데이터셋
uspto-grants-2010_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07838524B2

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