5-Chloro-2-fluoroaniline → HCID 58314469, 화합물

HRID 624825노트

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HRID 624825 반응식
Cl[C:2]1[CH:7]=[C:6]([N:8]([CH2:16][CH:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH3:18])C(=O)OC(C)(C)C)[N:5]2[N:25]=[CH:26][CH:27]=[C:4]2[N:3]=1.[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([F:36])=[C:33]([CH:35]=1)[NH2:34].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)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]>[Cl:28][C:29]1[CH:30]=[CH:31][C:32]([F:36])=[C:33]([NH:34][C:2]2[CH:7]=[C:6]([NH:8][CH2:16][CH:17]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)[CH3:18])[N:5]3[N:25]=[CH:26][CH:27]=[C:4]3[N:3]=2)[CH:35]=1

참가 물질

6

반응물 4

HCID 750155-Chloro-2-fluoroanilineHCID 2733832Lithium HexamethyldisilazideHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 86654660HCID 86654660, 화합물

생성물 1

HCID 58314469HCID 58314469, 화합물수율 21%

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

실험 절차

To tert-butyl 5-chloropyrazolo[1,5-a]pyrimidin-7-yl(2-morpholinopropyl)carbamate (396 mg, 1 mmol), 5-chloro-2-fluoroaniline (145 uL, 1.2 mmol), and LiHMDS (2.2 mL, 2.2 mmol, 1M in THF) was added X-Phos (11 mg, 0.024 mmol) and tris(dibenzylideneacetone)dipalladium(0) (18 mg, 0.02 mmol). The mixture was sealed and irradiated at 65° C. for 60 min in the microwave. The reaction was quenched with 1N HCL (2 mL) and then neutralized with saturated sodium bicarbonate solution. The mixture was extracted with ethyl acetate and washed with saturated sodium chloride solution. The organic layer was collected, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. The crude residue was dissolved in dichloromethane (2 mL) and trifluoroacetic acid (2 mL). After stirring at room temperature for 1 hour, the solution was concentrated under a stream of nitrogen. The crude material was neutralized with saturated sodium bicarbonate solution then purified by silica gel chromatography (75% ethyl acetate/hexanes) to yield the product, N5-(5-chloro-2-fluorophenyl)-N7-(2-morpholinopropyl)pyrazolo[1,5-a]pyrimidine-5,7-diamine (84 mg, 21% yield). LCMS (M+1=405)

후처리

  1. customThe mixture was sealed
  2. customirradiated at 65° C. for 60 min in the microwave
  3. customThe reaction was quenched with 1N HCL (2 mL)
  4. extractionThe mixture was extracted with ethyl acetate
  5. washwashed with saturated sodium chloride solution
  6. customThe organic layer was collected
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated to dryness
  10. dissolutionThe crude residue was dissolved in dichloromethane (2 mL)
  11. concentrationthe solution was concentrated under a stream of nitrogen
  12. customthen purified by silica gel chromatography (75% ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-f0c97c3903fe4c6797d83887caa7e58e
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09303033B2

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