Triethylamine → tert-Butyl 4-(4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 1473060노트

반응식

HRID 1473060 반응식
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][C:10]([O:12][CH3:13])=[O:11])#[CH:2].C(N(CC)CC)C.Cl[C:22]1[C:27]([C:28]([F:31])([F:30])[F:29])=[CH:26][N:25]=[C:24]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([CH:39]3[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH2:40]3)=[CH:35][CH:34]=2)[N:23]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C)C=O.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:13][O:12][C:10](=[O:11])[CH2:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=1[C:1]#[C:2][C:26]1[C:27]([C:28]([F:29])([F:30])[F:31])=[CH:22][N:23]=[C:24]([NH:32][C:33]2[CH:38]=[CH:37][C:36]([CH:39]3[CH2:40][CH2:41][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:43][CH2:44]3)=[CH:35][CH:34]=2)[N:25]=1

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 45789861Methyl 2-(2-ethynylphenyl)acetateHCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

생성물 1

HCID 71209070tert-Butyl 4-(4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
120 °C

실험 절차

A solution of methyl 2-(2-ethynylphenyl)acetate (I4) (0.069 g, 0.394 mmol) in dimethylformamide (2 mL) and triethylamine (0.183 mL, 1.31 mmol) was added to a mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I45) (0.150 g, 0.328 mmol), Pd(PPh3)2Cl2 (0.023 g, 0.033 mmol), Cu(I)I (0.0090 g, 0.049 mmol) and triphenylphosphine (0.013 g, 0.049 mmol) in dimethylformamide (2 mL). The reaction mixture was heated under microwave irradiation at 120° C. for 15 minutes. The reaction was cooled and the mixture diluted with EtOAc and passed through a plug of celite and washed through with ethyl acetate (50 mL). Water (50 mL) was added and the layers separated. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water (50 mL) and brine (50 mL) and dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a dark brown residue. The residue was purified by column chromatography on silica gel (0-20% EtOAc in cyclohexane) to yield the title compound (I46) (0.157 g, 80%) as a brown viscous oil.

후처리

  1. temperatureThe reaction was cooled
  2. washwashed through with ethyl acetate (50 mL)
  3. additionWater (50 mL) was added
  4. customthe layers separated
  5. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  6. washThe combined organic extracts were washed with water (50 mL) and brine (50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration the solvent
  9. customwas removed under reduced pressure
  10. customto give a dark brown residue
  11. customThe residue was purified by column chromatography on silica gel (0-20% EtOAc in cyclohexane)

출처 및 근거

ORD 기록
ord-2aff01e664cd4fbda512a95c65865022
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012461B2

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