Cesium carbonate → 4-[6-(7-Cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester

HRID 1483144노트

반응식

HRID 1483144 반응식
[CH3:1][N:2]([CH3:20])[C:3]([C:5]1[N:14]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10](Cl)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:35]=[N:36][C:37]([NH2:40])=[CH:38][CH:39]=2)[C:30](=[O:41])[CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(=O)([O-])[O-].[Cs+].[Cs+]>O1C=COC=C1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][N:31]([C:34]2[CH:35]=[N:36][C:37]([NH:40][C:10]3[N:11]=[CH:12][C:7]4[CH:6]=[C:5]([C:3](=[O:4])[N:2]([CH3:20])[CH3:1])[N:14]([CH:15]5[CH2:19][CH2:18][CH2:17][CH2:16]5)[C:8]=4[N:9]=3)=[CH:38][CH:39]=2)[C:30](=[O:41])[CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

참가 물질

7

반응물 3

HCID 10796Cesium carbonateHCID 583154322-Chloro-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamideHCID 59290959Tert-butyl 4-(6-aminopyridin-3-yl)-3-oxopiperazine-1-carboxylate

생성물 1

HCID 672413274-[6-(7-Cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester수율 92.5%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매2회HCID 634876Binap, (A+-)-촉매2회HCID 789681,4-Dioxin용매

반응 조건

온도
100 °C

실험 절차

A mixture of 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (225 mg, 0.77 mmol), 4-(6-aminopyridin-3-yl)-3-oxopiperazine-1-carboxylic acid tert-butyl ester (204 mg, 0.69 mmol), BINAP (24 mg, 0.038 mmol), palladium(II) acetate (6 mg, 0.027 mmol) and cesium carbonate (340 mg, 1.05 mmol) in dioxin (4 mL) is flushed with nitrogen and heated to 100° C. overnight. Additional palladium(II) acetate (6 mg, 0.027 mmol) and BINAP (24 mg, 0.038) are added and heating is continued at 110° C. for 2 h at which point LCMS and TLC analysis indicates completion of the reaction. The solvent is removed in vacuo and the residue is stirred in water with sonication in an ultrasonic bath. The suspension is filtered and the filter cake is washed with heptane. Drying in vacuo provides 4-[6-(7-Cyclopentyl-6-dimethylcarbamoyl-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-3-oxo-piperazine-1-carboxylic acid tert-butyl ester as a tan solid (350 mg, 83%) MS (ESI) m/z=549 [M+H]+.

후처리

  1. customis flushed with nitrogen
  2. temperatureheating
  3. customcompletion of the reaction
  4. customThe solvent is removed in vacuo
  5. filtrationThe suspension is filtered
  6. washthe filter cake is washed with heptane
  7. customDrying in vacuo

출처 및 근거

ORD 기록
ord-672b7d4affdc4381aa973fed2e06dab7
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09416136B2

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