Cesium carbonate → 7-(Cyclopropylamino)-5-(3,5-difluorophenylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde

HRID 624695노트

반응식

HRID 624695 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:9])[CH:8]=1)[NH2:5].C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:17]1[CH:22]=[C:21]([N:23]([CH:31]2[CH2:33][CH2:32]2)C(=O)OC(C)(C)C)[N:20]2[N:34]=[CH:35][C:36]([CH:37]=[O:38])=[C:19]2[N:18]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOCC>[CH:31]1([NH:23][C:21]2[N:20]3[N:34]=[CH:35][C:36]([CH:37]=[O:38])=[C:19]3[N:18]=[C:17]([NH:5][C:4]3[CH:3]=[C:2]([F:1])[CH:8]=[C:7]([F:9])[CH:6]=3)[CH:22]=2)[CH2:32][CH2:33]1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 965953,5-DifluoroanilineHCID 634876Binap, (A+-)-HCID 58196421Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate

생성물 1

HCID 583143057-(Cyclopropylamino)-5-(3,5-difluorophenylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde수율 80%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 3283Diethyl Ether용매HCID 312751,4-Dioxane용매

실험 절차

3,5-Difluoroaniline (29 mg, 0.22 mmol), Cs2CO3 (67 mg, 0.21 mmol) were added to Tert-butyl 5-chloro-3-formylpyrazolo[1,5-a]pyrimidin-7-yl(cyclopropyl)carbamate (50 mg, 0.15 mmol) dissolved in 1,4-dioxane (1 mL). Racemic BINAP (6 mg, 0.06 mmol) and palladium(II) acetate (4 mg, 0.04 mmol) were then added. The mixture was sealed and irradiated at 110° C. for 20 min in the microwave. Et2O (3 mL) was added and the solution was filtered. The filtrate was concentrated in vacuo. The crude residue was dissolved in dichloromethane (1.5 mL) and trifluoroacetic acid (1.5 mL). After 1 h, the solution was concentrated under a stream of air. The residue was triturated with 20% 2-propanol/hexanes. The product was filtered to yield 7-(cyclopropylamino)-5-(3,5-difluorophenylamino)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde (39 mg, 80%). LCMS (M+1=330)

후처리

  1. customThe mixture was sealed
  2. customirradiated at 110° C. for 20 min in the microwave
  3. filtrationthe solution was filtered
  4. concentrationThe filtrate was concentrated in vacuo
  5. dissolutionThe crude residue was dissolved in dichloromethane (1.5 mL)
  6. concentrationthe solution was concentrated under a stream of air
  7. customThe residue was triturated with 20% 2-propanol/hexanes
  8. filtrationThe product was filtered

출처 및 근거

ORD 기록
ord-38813bad27a24948b4906a13d92a2a86
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09303033B2

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