Triethylamine → 3-[4-(Azetidin-1-ylcarbonyl)-2,5-difluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 20599

반응식

HRID 20599 반응식
[F:1][C:2]1[CH:10]=[C:9](F)[C:8]([F:12])=[CH:7][C:3]=1[C:4]([OH:6])=O.ClC(N(C)C)=C(C)C.C(N(CC)CC)C.Cl.[NH:29]1[CH2:32][CH2:31][CH2:30]1.[OH:33][C:34]1[CH:35]=[C:36]([CH:46]=[C:47]([O:49][C@@H:50]([CH3:53])[CH2:51][OH:52])[CH:48]=1)[C:37]([NH:39][C:40]1[CH:44]=[CH:43][N:42]([CH3:45])[N:41]=1)=[O:38].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.Cl.C(#N)C>[N:29]1([C:4]([C:3]2[C:2]([F:1])=[CH:10][C:9]([O:33][C:34]3[CH:35]=[C:36]([CH:46]=[C:47]([O:49][C@@H:50]([CH3:53])[CH2:51][OH:52])[CH:48]=3)[C:37]([NH:39][C:40]3[CH:44]=[CH:43][N:42]([CH3:45])[N:41]=3)=[O:38])=[C:8]([F:12])[CH:7]=2)=[O:6])[CH2:32][CH2:31][CH2:30]1

참가 물질

10

반응물 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 5211702,4,5-Trifluorobenzoic acidHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 12308726Azetidine hydrochlorideHCID 593468923-Hydroxy-5-{[(S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide

생성물 1

HCID 116128053-[4-(Azetidin-1-ylcarbonyl)-2,5-difluorophenoxy]-5-[(1S)-2-hydroxy-1-methylethoxy]-N-(1-methyl-1H-pyrazol-3-yl)benzamide수율 31.9%

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매2회

반응 조건

온도
160 °C

실험 절차

A solution of 2,4,5-trifluorobenzoic acid (123 mg, 0.7 mmol) in DCM (1.7 mL) was treated with (1-chloro-2-methylprop-1-en-1-yl)dimethylamine (103 mg, 0.77 mmol) and stirred under argon for 1 hour. The mixture was then treated with triethylamine (0.29 mL, 2.1 mmol) and azetidine hydrochloride (78 mg, 0.84 mmol), before being left to stir for 18 hours. The mixture was diluted with DCM (5 mL) and 2M hydrochloric acid (4 mL) and separated. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was treated with suspension of 3-hydroxy-5-{[(1S)-2-hydroxy-1-methylethyl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)benzamide (200 mg, 0.477 mmol) and potassium carbonate (284 mg, 2.05 mmol) in acetonitrile (3.5 mL) was heated in a microwave reactor at 160° C. for 1.5 hours. The reaction mixture was filtered and concentrated in vacuo. The residue was then chromatographed on silica, eluting with 0-15% methanol in ethylacetate, to give the title compound (74 mg).

후처리

  1. waitbefore being left
  2. stirringto stir for 18 hours
  3. customseparated
  4. dry with materialThe organic layer was dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationThe reaction mixture was filtered
  8. concentrationconcentrated in vacuo
  9. customThe residue was then chromatographed on silica
  10. washeluting with 0-15% methanol in ethylacetate

출처 및 근거

ORD 기록
ord-ef98e1c7b4764eec9a3f724e10aa14e9
출처 데이터셋
uspto-grants-2010_06
특허 번호
US07745475B2

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