Water → 6-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carboxylic acid ethyl ester

HRID 2368210ノート

反応式

HRID 2368210 の反応式
[CH2:1]([O:3][C:4]([C:6]1[C:11]([NH2:12])=[CH:10][CH:9]=[C:8]([CH:13]2[CH2:15][CH2:14]2)[N:7]=1)=[O:5])[CH3:2].Br[C:17]1[CH:18]=[N:19][CH:20]=[N:21][CH:22]=1.O.C(=O)([O-])[O-].[K+].[K+]>CC1C=CC=CC=1C.ClCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[C:11]([NH:12][C:17]2[CH:18]=[N:19][CH:20]=[N:21][CH:22]=2)=[CH:10][CH:9]=[C:8]([CH:13]2[CH2:14][CH2:15]2)[N:7]=1)=[O:5])[CH3:2]

参加物

9

反応物 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 783445-BromopyrimidineHCID 67299907Ethyl 3-amino-6-cyclopropylpicolinate

生成物 1

HCID 583680566-Cyclopropyl-3-(pyrimidin-5-ylamino)-pyridine-2-carboxylic acid ethyl ester収率 75.7%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)触媒HCID 6344Dichloromethane溶媒HCID 7237O-Xylene溶媒

反応条件

温度
140 °C

実験手順

A suspension of 3-amino-6-cyclopropylpyridine-2-carboxylic acid ethyl ester (763 mg, 3.7 mmol), 5-bromopyrimidine (823 mg, 5.2 mmol), water (140 μl, 7.8 mmol) and potassium carbonate (920 mg, 6.7 mmol) in o-xylene (10 ml) was evacuated and vented with argon. Palladium(II) acetate (33 mg, 0.15 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xantphos; 107 mg, 0.18 mmol) were consecutively added under inert gas atmosphere and the reaction mixture was heated to 140° C. and stirred overnight. After cooling-down to ambient temperature, the reaction mixture was diluted with dichloromethane (15 ml) and filtrated. The filtrate was concentrated in vacuo and the product was purified by silica gel chromatography using a heptane/ethyl acetate gradient to yield the title compound (796 mg, 75.7%) as light yellow solid.

後処理

  1. customwas evacuated
  2. filtrationfiltrated
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe product was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-d0fa443a83504464ab6d04fbfa1da7f0
出典データセット
uspto-grants-2014_04
特許番号
US08703768B2

反応ノート

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