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Binap, (A+-)- → 2-[6-((3R,6R)-5-{[Bis-(4-methoxy-phenyl)-phenyl-methyl]-amino}-3,6-dimethyl-6-trifluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-5-fluoro-pyridin-2-ylamino]-nicotinonitrile

HRID 925465
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HRID 925465 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[C@:26]([CH3:44])([C:40]([F:43])([F:42])[F:41])[O:27][CH2:28][C@:29]([C:32]3[C:37]([F:38])=[CH:36][CH:35]=[C:34](Br)[N:33]=3)([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.[NH2:45][C:46]1[C:51]([C:52]#[N:53])=[CH:50][CH:49]=[CH:48][N:47]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([NH:24][C:25]2[C@:26]([CH3:44])([C:40]([F:43])([F:42])[F:41])[O:27][CH2:28][C@:29]([C:32]3[N:33]=[C:34]([NH:45][C:46]4[N:47]=[CH:48][CH:49]=[CH:50][C:51]=4[C:52]#[N:53])[CH:35]=[CH:36][C:37]=3[F:38])([CH3:31])[N:30]=2)([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5][CH:4]=1
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 634876Binap, (A+-)-HCID 8182592-Amino-3-cyanopyridineHCID 23676156Sodium t-butoxideHCID 89500352[Bis-(4-methoxy-phenyl)-phenyl-methyl]-[(2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-amine

생성물 1

HCID 90387331
2-[6-((3R,6R)-5-{[Bis-(4-methoxy-phenyl)-phenyl-methyl]-amino}-3,6-dimethyl-6-trifluoromethyl-3,6-dihydro-2H-[1,4]oxazin-3-yl)-5-fluoro-pyridin-2-ylamino]-nicotinonitrile

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
100 °C

실험 절차

To a solution of [bis-(4-methoxy-phenyl)-phenyl-methyl]-[(2R,5R)-5-(6-bromo-3-fluoro-pyridin-2-yl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-amine (250 mg, 0.372 mmol) in toluene (3.72 ml) was added 2-amino-3-pyridinecarbonitrile (221 mg, 1.859 mmol), Pd2(dba)3 (6.81 mg, 7.43 μmol), BINAP (9.26 mg, 0.015 mmol) and sodium tert-butoxide (50 mg, 0.520 mmol). The reaction mixture was degassed for 5 min and the microwave vial was sealed and stirred at 100° C. for 9 h. The reaction mixture was diluted with DCM and washed with water. The organic layer was dried with Na2SO4. The residue was purified by chromatography (silica gel; eluent DCM/MeOH+NH4OH) to afford the title compound.

후처리

  1. customThe reaction mixture was degassed for 5 min
  2. customthe microwave vial was sealed
  3. additionThe reaction mixture was diluted with DCM
  4. washwashed with water
  5. dry with materialThe organic layer was dried with Na2SO4
  6. customThe residue was purified by chromatography (silica gel; eluent DCM/MeOH+NH4OH)

출처 및 근거

ORD 기록
ord-df6dc3d85fc5496fb3e6c86391c95af7
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09284284B2

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