Potassium Phosphate, Tribasic → 2-hydroxy-2-methyl-N-(2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)propanamide

HRID 715480ノート

反応式

HRID 715480 の反応式
Cl[C:2]1[C:7]2[CH2:8][N:9]([CH:12]([C:14]3[CH:15]=[N:16][C:17]([O:21][CH2:22][C:23]([F:26])([F:25])[F:24])=[C:18]([CH3:20])[CH:19]=3)[CH3:13])[C:10](=[O:11])[C:6]=2[CH:5]=[CH:4][N:3]=1.C([O:30][C:31]([CH3:36])([CH3:35])[C:32]([NH2:34])=[O:33])(=O)C.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]>[OH:30][C:31]([CH3:36])([CH3:35])[C:32]([NH:34][C:2]1[C:7]2[CH2:8][N:9]([CH:12]([C:14]3[CH:15]=[N:16][C:17]([O:21][CH2:22][C:23]([F:25])([F:26])[F:24])=[C:18]([CH3:20])[CH:19]=3)[CH3:13])[C:10](=[O:11])[C:6]=2[CH:5]=[CH:4][N:3]=1)=[O:33]

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 124355421-Amino-2-methyl-1-oxopropan-2-yl acetateHCID 898749364-chloro-2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one

生成物 1

HCID 898743012-hydroxy-2-methyl-N-(2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-1-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-4-yl)propanamide収率 31%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
170 °C

実験手順

A mixture of 4-chloro-2-(1-(5-methyl-6-(2,2,2-trifluoroethoxy)pyridin-3-yl)ethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-1-one (20 mg, 0.052 mmol, Intermediate-2, single enantiomer), 1-amino-2-methyl-1-oxopropan-2-yl acetate (15 mg, 0.10 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 volatiles are removed. The residue is dissolved in THF (1.0 mL) and 2 M aqueous sodium hydroxide solution (0.50 mL) is added, and the mixture is stirred overnight at rt. The mixture is neutralized by the addition of 2 M hydrochloric acid (0.50 mL), diluted with THF (4.0 mL) and extracted with EtOAc. The separated organic layer is dried over sodium sulfate and concentrated in vacuo. The mixture is purified by a strong cation exchange cartridge (BondElute™ SCX, 1 g/6 mL, Varian Inc.) and then by preparative LC-MS to give 7.2 mg (31% yield) of the title compound.

後処理

  1. filtrationThe reaction mixture is filtered through a short column of NH-gel
  2. washeluting with EtOAc and volatiles
  3. customare removed
  4. dissolutionThe residue is dissolved in THF (1.0 mL)
  5. addition2 M aqueous sodium hydroxide solution (0.50 mL) is added
  6. additionThe mixture is neutralized by the addition of 2 M hydrochloric acid (0.50 mL)
  7. additiondiluted with THF (4.0 mL)
  8. extractionextracted with EtOAc
  9. dry with materialThe separated organic layer is dried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe mixture is purified by a strong cation exchange cartridge (BondElute™ SCX, 1 g/6 mL, Varian Inc.)

出典と根拠

ORDレコード
ord-3869b9847250477eaf9a77bf27489be4
出典データセット
uspto-grants-2015_11
特許番号
US09187475B2

反応ノート

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