Potassium Carbonate → 4-(2,3-Difluoro-phenylamino)-6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-pyrimidine-5-carbonitrile

HRID 1426074노트

반응식

HRID 1426074 반응식
Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[F:11][C:12]1[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:13]=1[NH2:14].C([O-])([O-])=O.[K+].[K+].[CH:26]([C:29]1[N:33]=[C:32]([CH:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)[O:31][N:30]=1)([CH3:28])[CH3:27]>CN(C=O)C.O.CCOC(C)=O>[F:11][C:12]1[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:13]=1[NH:14][C:2]1[C:7]([C:8]#[N:9])=[C:6]([N:37]2[CH2:36][CH2:35][CH:34]([C:32]3[O:31][N:30]=[C:29]([CH:26]([CH3:28])[CH3:27])[N:33]=3)[CH2:39][CH2:38]2)[N:5]=[CH:4][N:3]=1

참가 물질

8

반응물 4

HCID 11430Potassium Carbonate2회HCID 782782,3-DifluoroanilineHCID 5993714,6-Dichloropyrimidine-5-carbonitrileHCID 242088454-(3-(Propan-2-yl)-1,2,4-oxadiazol-5-yl)piperidine

생성물 1

HCID 582165364-(2,3-Difluoro-phenylamino)-6-[4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidin-1-yl]-pyrimidine-5-carbonitrile

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

To a solution of 4,6-dichloro-pyrimidine-5-carbonitrile (254 mg, 1.47 mmol) and 2,3-difluoroaniline (190 mg, 1.47 mmol) in DMF (3 mL) at 0° C. was added K2CO3 (203 mg, 1.47 mmol). The completion of the reaction was monitored by TLC (EtOAc:Hex 1:1, Rf=0.90). After the completion of the reaction, 4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-piperidine (340 mg, 1.47 mmol) and K2CO3 (406 mg, 2.94 mmol) were added at 0° C. The reaction was warmed to rt and stirred for 30 min. The reaction was heated to 40° C. and maintained for 1 h. The reaction was cooled to rt, poured in to H2O (50 mL) and extracted with EtOAc (50 mL, two times). The EtOAc was dried over MgSO2 and concentrated under vacuum. The crude product was purified over SiO2 (EtOAc:Hex=1:1, Rf=0.49) to afford Compound B130 (501 mg; 76.7%). 1H-NMR (DMSO-d6): 9.60 (1H, s), 8.28 (1H, s), 7.45˜7.29 (3H, m), 4.64 (2H, m), 3.59˜3.52 (4H, m), 3.41˜3.49 (2H, m), 2.29˜2.25 (2H, b), 1.96˜1.86 (2H, m), 1.39 (6H, d) ppm. LCMS: 426.43.

후처리

  1. additionwere added at 0° C
  2. temperatureThe reaction was heated to 40° C.
  3. temperaturemaintained for 1 h
  4. temperatureThe reaction was cooled to rt
  5. extractionextracted with EtOAc (50 mL, two times)
  6. dry with materialThe EtOAc was dried over MgSO2
  7. concentrationconcentrated under vacuum
  8. customThe crude product was purified over SiO2 (EtOAc:Hex=1:1, Rf=0.49)
  9. customto afford Compound B130 (501 mg; 76.7%)

출처 및 근거

ORD 기록
ord-101afa2c48d743b8b422724f5defc3e2
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08933083B2

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