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

HRID 467613노트

반응식

HRID 467613 반응식
[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]

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 167845palladium(II) acetate촉매HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 6344Dichloromethane용매HCID 7237O-Xylene용매

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온도
140 °C

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-f796e15947cf4bbba926ad523b51ce7a
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08623866B2

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