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

HRID 1426074ノート

反応式

HRID 1426074 の反応式
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

参加物

8

反応物 4

HCID 11430Potassium Carbonate2 回HCID 782782,3-DifluoroanilineHCID 5993714,6-Dichloropyrimidine-5-carbonitrileHCID 242088454-(3-(Propan-2-yl)-1,2,4-oxadiazol-5-yl)piperidine

生成物 1

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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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%)

出典と根拠

ORDレコード
ord-101afa2c48d743b8b422724f5defc3e2
出典データセット
uspto-grants-2015_01
特許番号
US08933083B2

反応ノート

読み込み中…