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 385852노트

반응식

HRID 385852 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-8465d6fa78bf459db1c3ff87b284b51c
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367706B2

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