Potassium Phosphate, Tribasic → N-(1-oxo-2-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)isobutyramide

HRID 715479노트

반응식

HRID 715479 반응식
Cl[C:2]1[C:7]2[CH2:8][N:9]([CH:12]([C:14]3[CH:15]=[N:16][C:17]([O:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:18][CH:19]=3)[CH3:13])[C:10](=[O:11])[C:6]=2[CH:5]=[CH:4][N:3]=1.[C:26]([NH2:31])(=[O:30])[CH:27]([CH3:29])[CH3:28].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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]>[O:11]=[C:10]1[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:31][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[C:7]=2[CH2:8][N:9]1[CH:12]([C:14]1[CH:15]=[N:16][C:17]([O:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:18][CH:19]=1)[CH3:13]

참가 물질

7

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 68424IsobutyramideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 898745024-chloro-2-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one2회

생성물 1

HCID 72195303N-(1-oxo-2-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)isobutyramide수율 32%

시약·촉매·용매 2

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

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온도
170 °C

실험 절차

A mixture of 4-chloro-2-(1-(6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one (20 mg, 0.054 mmol, Intermediate 1, single enantiomer), isobutyramide (9.0 mg, 0.11 mmol), tris(dibenzylideneacetone)dipalladium(0) (5 mg, 5.2 micro mol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (9.0 mg, 0.016 mmol) and tripotassium phosphate (16 mg, 0.075 mmol) in dioxane (2 mL) is heated at 170° C. for 40 min by microwave irradiation. The reaction mixture is filtered through a short column of NH-gel eluting with EtOAc and the filtrate is concentrated. The residue is purified by a strong cation exchange cartridge (BondElute™ SCX, 1 g/6 mL, Varian Inc.) and then by preparative LC-MS to give 7.3 mg (32% yield) of the title compound.

후처리

  1. filtrationThe reaction mixture is filtered through a short column of NH-gel
  2. washeluting with EtOAc
  3. concentrationthe filtrate is concentrated
  4. customThe residue is purified by a strong cation exchange cartridge (BondElute™ SCX, 1 g/6 mL, Varian Inc.)

출처 및 근거

ORD 기록
ord-b30a7591214147639bda96638efb2cb9
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09187475B2

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