1,2-Dichloroethane → HCID 57955324, 화합물

HRID 1094912노트

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HRID 1094912 반응식
N#N.[NH2:3][C:4]1[C:9]2=[C:10]([C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29]([NH:31][C:32]4[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][C:33]=4[F:42])=[O:30])=[C:24]([F:43])[CH:23]=3)[C:11]([CH2:19][O:20][CH3:21])=[C:12]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[N:8]2[N:7]=[CH:6][N:5]=1.ClCCCl.[CH3:48][N:49]([CH3:53])[C:50](Cl)=[O:51]>O1CCCC1>[NH2:3][C:4]1[C:9]2=[C:10]([C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:30])[NH:31][C:32]4[CH:37]=[C:36]([C:38]([F:41])([F:39])[F:40])[CH:35]=[CH:34][C:33]=4[F:42])=[C:24]([F:43])[CH:23]=3)[C:11]([CH2:19][O:20][CH3:21])=[C:12]([CH:13]3[CH2:18][CH2:17][N:16]([C:50]([N:49]([CH3:53])[CH3:48])=[O:51])[CH2:15][CH2:14]3)[N:8]2[N:7]=[CH:6][N:5]=1

참가 물질

6

반응물 4

HCID 111,2-DichloroethaneHCID 947NitrogenHCID 6598Dimethylcarbamoyl ChlorideHCID 57955166HCID 57955166, 화합물

생성물 1

HCID 57955324HCID 57955324, 화합물수율 17.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a flask charged with N2 was added 1-{4-[4-amino-6-(methoxymethyl)-7-piperidin-4-ylpyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro-5-(trifluoro-methyl)phenyl]urea (Example 149) (30 mg, 0.052 mmol, 1.0 eq) and 1,2-dichloroethane (2 mL). Tetrahydrofuran was added dropwise until the reaction mixture was a complete solution. The solution was cooled to 0° C. and dimethylcarbamoyl chloride (4.7 μl, 1 eq) was added. The reaction mixture was allowed to gradually warm to rt over 17 hours. The reaction was concentrated and the residue dissolved in EtOAc. The organic phase was washed with saturated sodium bicarbonate solution (2×), brine (1×), separated and the organic layer dried (Na2SO4). The organic layer was filtered, concentrated and purified via flash column chromatography (6:4 tetrahydrofuran/hexanes). The purified fractions were collected, concentrated, stirred in hexanes and filtered. The filtrate was placed under vacuum overnight to yield the title compound (6 mg, 17.8% yield). 1H-NMR (DMSO-d6) δ 9.44 (s, 1H), 9.29 (s, 1H), 8.65 (d, J=6.5 Hz, 1H), 8.29 (t, J=8.5 Hz, 1H), 7.89 (s, 1H), 7.51 (t, J=9.9 Hz, 1H), 7.41 (m, 1H), 7.29 (dd, J=12.3, 1.7 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 4.23 (s, 2H), 3.68 (m, 2H), 3.44 (m, 1H), 3.16 (s, 3H), 2.75 (s, 6H), 2.26 (m, 2H), 1.64 (m, 2H); MS [M+H]+=647; LCMS RT=3.03 min.

후처리

  1. temperatureto gradually warm to rt over 17 hours
  2. concentrationThe reaction was concentrated
  3. dissolutionthe residue dissolved in EtOAc
  4. washThe organic phase was washed with saturated sodium bicarbonate solution (2×), brine (1×)
  5. customseparated
  6. dry with materialthe organic layer dried (Na2SO4)
  7. filtrationThe organic layer was filtered
  8. concentrationconcentrated
  9. custompurified via flash column chromatography (6:4 tetrahydrofuran/hexanes)
  10. customThe purified fractions were collected
  11. concentrationconcentrated
  12. filtrationfiltered
  13. customwas placed under vacuum overnight

출처 및 근거

ORD 기록
ord-5c56824ba54c4b14b534514624017189
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08133995B2

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