Cesium carbonate → 3-[2-(2-Isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-methoxypiperidine-1-carboxylic acid tert-butyl ester

HRID 1923316노트

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HRID 1923316 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([C:16]2[N:17]([CH3:32])[C:18]3[C:23]([N:24]=2)=[C:22]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[N:21]=[C:20](Cl)[N:19]=3)([O:14][CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:33]([C:36]1[NH:37][C:38]2[CH:44]=[CH:43][CH:42]=[CH:41][C:39]=2[N:40]=1)([CH3:35])[CH3:34].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[CH2:13][CH2:12][CH2:11][C:10]([C:16]2[N:17]([CH3:32])[C:18]3[C:23]([N:24]=2)=[C:22]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[N:21]=[C:20]([N:37]2[C:38]4[CH:44]=[CH:43][CH:42]=[CH:41][C:39]=4[N:40]=[C:36]2[CH:33]([CH3:35])[CH3:34])[N:19]=3)([O:14][CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 221212-(propan-2-yl)-1H-1,3-benzodiazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596053523-(2-Chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-3-methoxypiperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 596052973-[2-(2-Isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-methoxypiperidine-1-carboxylic acid tert-butyl ester수율 65.1%

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-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-3-methoxypiperidine-1-carboxylic acid tert-butyl ester (3.0 g, 6.42 mmol), 2-isopropylbenzimidazole (1.24 g, 7.71 mmol), tris(dibenzylideneacetone)dipalladium (150 mg, 0.16 mmol), XPhos (306 mg, 0.64 mmol) and Cs2CO3 (3.14 g, 9.64 mmol) in dioxane (50 mL) was purged with argon then heated at 110° C. for 16 h. The reaction mixture was partitioned between EtOAc and H2O, the organic phase washed with brine then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 30-70%) affording 3-[2-(2-Isopropylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]-3-methoxypiperidine-1-carboxylic acid tert-butyl ester (2.47 g, 65%). LCMS (method A): RT 3.52 min, [M+H]+ 591.5

후처리

  1. customwas purged with argon
  2. customThe reaction mixture was partitioned between EtOAc and H2O
  3. washthe organic phase washed with brine
  4. dry with materialthen dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si—PCC, EtOAc:cyclohexane, 30-70%)

출처 및 근거

ORD 기록
ord-0f3397889deb4ded80f0e29716ee6329
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08173650B2

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