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Methyl Isocyanate → 6-[2-(3-Methyl-ureido)-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

HRID 1094506
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HRID 1094506 반응식
[CH3:1][N:2]=[C:3]=[O:4].[F:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([C:15]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[CH:31]=[CH:30][N:29]=[C:28]([NH2:32])[N:27]=4)=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)=[O:14])=[CH:8][C:7]=1[C:33]([F:36])([F:35])[F:34]>C1COCC1.CCOC(C)=O.O>[F:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([C:15]2[C:24]3[C:19](=[CH:20][C:21]([O:25][C:26]4[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:3]([NH:2][CH3:1])=[O:4])[N:27]=4)=[CH:22][CH:23]=3)[CH:18]=[CH:17][CH:16]=2)=[O:14])=[CH:8][C:7]=1[C:33]([F:34])([F:36])[F:35]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

6

반응물 2

HCID 12228Methyl Isocyanate2회HCID 160715501-Naphthalenecarboxamide, 6-[(2-amino-4-pyrimidinyl)oxy]-N-[4-fluoro-3-(trifluoromethyl)phenyl]-

생성물 1

HCID 236528656-[2-(3-Methyl-ureido)-pyrimidin-4-yloxy]-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran
용매
HCID 8857Ethyl Acetate용매

실험 절차

130 μl (2.2 mMol) methyl isocyanate are added to a solution of 300 mg (0.68 mMol) 6-(2-amino-pyrimidin-4-yloxy)-naphthalene-1-carboxylic acid (4-fluoro-3-trifluoromethyl-phenyl)-amide (Step 10.3) in 10 ml THF in a sealed vessel. The mixture is stirred at 100° C. for 11 days (another 1.1 eq. of Me-NCO is added on day 8 and 9). Then the reaction mixture is diluted with EtOAc and water, the aq. phase separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and partially concentrated. Precipitation with hexane, filtration and re-crystallization from boiling THF/CH3CN gives the title compound: m.p.: 233-234° C.

후처리

  1. additionis added on day 8 and 9)
  2. customthe aq. phase separated off
  3. extractionextracted twice with EtOAc
  4. washThe organic layers are washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationpartially concentrated
  7. customPrecipitation
  8. filtrationwith hexane, filtration and re-crystallization

출처 및 근거

ORD 기록
ord-89a8a37433684e149257d1681d5f4657
출처 데이터셋
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08133886B2

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