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Cesium carbonate → 3-[2-(2-Ethylbenzoimidazol-1-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethylene]azetidine-1-carboxylic acid tert-butyl ester

HRID 1922789
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HRID 1922789 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=[CH:12][C:13]2[S:21][C:20]3[C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[N:18][C:17](Cl)=[N:16][C:15]=3[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:29]([C:31]1[NH:32][C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=1)[CH3:30].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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:1]([O:5][C:6]([N:8]1[CH2:11][C:10](=[CH:12][C:13]2[S:21][C:20]3[C:19]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[N:18][C:17]([N:32]4[C:33]5[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=5[N:35]=[C:31]4[CH2:29][CH3:30])=[N:16][C:15]=3[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
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참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 158072-EthylbenzimidazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596057503-(2-Chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethylene)azetidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 596056083-[2-(2-Ethylbenzoimidazol-1-yl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethylene]azetidine-1-carboxylic acid tert-butyl ester
수율 112.2%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

A mixture of 3-(2-chloro-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-ylmethylene)azetidine-1-carboxylic acid tert-butyl ester (1.1 g, 2.51 mmol), 2-ethylbenzimidazole (400 mg, 2.74 mmol), tris(dibenzylideneacetone)dipalladium (115 mg, 0.13 mmol), XPhos (240 mg, 0.50 mmol) and Cs2CO3 (1.25 g, 3.84 mmol) in dioxane (25 mL) was purged with argon then heated at 110° C. for 16 h. The reaction mixture was filtered through Celite®, washing with DCM, and the filtrate concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%) affording the title compound as an orange solid (1.5 g, quant.). LCMS (method A): RT 3.40 min [M+H]+ 533.4

후처리

  1. customwas purged with argon
  2. filtrationThe reaction mixture was filtered through Celite®
  3. washwashing with DCM
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-10%)

출처 및 근거

ORD 기록
ord-04900977e226495c885d5a7c6b31c4e9
출처 데이터셋
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08173650B2

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