2-Methyl-2-butanol → 5-[4-(3-Fluorooxetan-3-yl)phenyl]-2-({6-[(2-hydroxy-2-methylpropoxy)methyl]pyridin-2-yl}amino)thiophene-3-carboxamide

HRID 385852ノート

反応式

HRID 385852 の反応式
[NH2:1][C:2]1[S:3][C:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3([F:20])[CH2:19][O:18][CH2:17]3)=[CH:12][CH:11]=2)=[CH:5][C:6]=1[C:7]([NH2:9])=[O:8].Br[C:22]1[N:27]=[C:26]([CH2:28][O:29][CH2:30][C:31]([CH3:34])([OH:33])[CH3:32])[CH:25]=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(O)(CC)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:20][C:16]1([C:13]2[CH:14]=[CH:15][C:10]([C:4]3[S:3][C:2]([NH:1][C:22]4[CH:23]=[CH:24][CH:25]=[C:26]([CH2:28][O:29][CH2:30][C:31]([OH:33])([CH3:32])[CH3:34])[N:27]=4)=[C:6]([C:7]([NH2:9])=[O:8])[CH:5]=3)=[CH:11][CH:12]=2)[CH2:17][O:18][CH2:19]1

参加物

7

反応物 5

HCID 64052-Methyl-2-butanolHCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 583352721-[(6-Bromopyridin-2-yl)methoxy]-2-methylpropan-2-olHCID 595262372-Amino-5-[4-(3-fluorooxetan-3-yl)phenyl]thiophene-3-carboxamide

生成物 1

HCID 595261425-[4-(3-Fluorooxetan-3-yl)phenyl]-2-({6-[(2-hydroxy-2-methylpropoxy)methyl]pyridin-2-yl}amino)thiophene-3-carboxamide

試薬・触媒・溶媒 1

HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
100 °C

実験手順

2-Amino-5-[4-(3-fluorooxetan-3-yl)phenyl]thiophene-3-carboxamide (88 mg, 0.301 mmol), 1-[(6-bromopyridin-2-yl)methoxy]-2-methylpropan-2-ol (Example 217 Step 1) (78 mg, 0.301 mmol), Pd2dba3 (27.6 mg, 0.030 mmol), K2CO3 (45.8 mg, 0.331 mmol) and X-Phos (71.8 mg, 0.151 mmol) were added to a 5 mL microwave vial. Degassed tert-amyl alcohol (0.6 mL) was added and the vial evacuated and back-filled with N2 (3×). The resulting mixture was stirred at 100° C. overnight. After cooling to room temperature, the mixture was diluted with methanol, silica gel was added, and the solvent was removed in vacuo. Purification of the residue by flash chromatography (silica, 0-10% MeOH-DCM) followed by flash chromatography (silica, 12-100% EtOAc-hexanes) gave the title compound as a pale yellow solid.

後処理

  1. customthe vial evacuated
  2. additionback-filled with N2 (3×)
  3. temperatureAfter cooling to room temperature
  4. additionthe mixture was diluted with methanol, silica gel
  5. additionwas added
  6. customthe solvent was removed in vacuo
  7. customPurification of the residue by flash chromatography (silica, 0-10% MeOH-DCM)

出典と根拠

ORDレコード
ord-8465d6fa78bf459db1c3ff87b284b51c
出典データセット
uspto-grants-2013_02
特許番号
US08367706B2

反応ノート

読み込み中…