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Cesium carbonate → tert-Butyl 4-(4-(tert-butoxycarbonylamino)naphthalen-1-yloxy)pyrimidin-2-ylcarbamate

HRID 2069150
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HRID 2069150 반응식
[C:1](=[O:8])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[NH2:2].Cl[C:10]1[N:15]=[C:14]([O:16][C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[C:20]([NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:19][CH:18]=2)[CH:13]=[CH:12][N:11]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1COCC1.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]>[C:30]([O:29][C:28]([NH:27][C:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:17]([O:16][C:14]2[CH:13]=[CH:12][N:11]=[C:10]([NH:2][C:1](=[O:8])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])[N:15]=2)=[CH:18][CH:19]=1)=[O:34])([CH3:33])([CH3:32])[CH3:31]
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참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 86660490tert-Butyl 4-(2-chloropyrimidin-4-yloxy)naphthalen-1-ylcarbamate

생성물 1

HCID 68322851tert-Butyl 4-(4-(tert-butoxycarbonylamino)naphthalen-1-yloxy)pyrimidin-2-ylcarbamate수율 56.1%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8028Tetrahydrofuran용매

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온도
75 °C

실험 절차

To a degassed suspension of tert-butyl carbamate (1.89 g, 16.1 mmol), tert-butyl 4-(2-chloropyrimidin-4-yloxy)naphthalen-1-ylcarbamate (2.00 g, 5.38 mmol), Cs2CO3 (4.38 g, 13.45 mmol) and Xanthphos (0.249 g, 0.430 mmol) in THF (50 mL) was added Pd2dba3 (197 mg, 0.215 mmol) and the reaction mixture was heated at 75° C. for 16 hr. The reaction mixture was cooled to RT and was partitioned between EtOAc (40 mL) and water (40 mL). The aq layer was separated and extracted with EtOAc (40 mL) and the combined organic extracts were dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, EtOAc in isohexane, 15-60%, gradient elution to afford the title compound as an off-white solid (1.365 g 53%.); Rt 2.53 min (Method 2); m/z 453 (M+H)+, (ES+)+

후처리

  1. temperatureThe reaction mixture was cooled to RT
  2. customwas partitioned between EtOAc (40 mL) and water (40 mL)
  3. customThe aq layer was separated
  4. extractionextracted with EtOAc (40 mL)
  5. dry with materialthe combined organic extracts were dried (MgSO4)
  6. customevaporated in vacuo
  7. customThe residue was purified by flash column chromatography (
  8. washSiO2, EtOAc in isohexane, 15-60%, gradient elution

출처 및 근거

ORD 기록
ord-77d3cc6dd3ad404a874a7ccda7500e74
출처 데이터셋
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08299074B2

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