1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → (S)-2-(biphenyl-4-ylmethyl)-7-isobutyl-5-methyl-3-(pyrrolidin-3-ylamino)-2H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione

HRID 81415

반응식

HRID 81415 반응식
[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:16](Cl)=[C:15]3[C:10]([N:11]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:12](=[O:20])[N:13]([CH3:19])[C:14]3=[O:18])=[N:9]2)=[CH:3][CH:2]=1.[NH2:31][C@H:32]1[CH2:36][CH2:35][N:34](C(OC(C)(C)C)=O)[CH2:33]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(O[K])(C)(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]>[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[C:16]([NH:31][C@H:32]3[CH2:36][CH2:35][NH:34][CH2:33]3)=[C:15]3[C:10]([N:11]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:12](=[O:20])[N:13]([CH3:19])[C:14]3=[O:18])=[N:9]2)=[CH:3][CH:2]=1

참가 물질

6

반응물 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 685083002-(biphenyl-4-ylmethyl)-3-chloro-7-isobutyl-5-methyl-2H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dioneHCID 178418922HCID 178418922, 화합물

생성물 1

HCID 42640996(S)-2-(biphenyl-4-ylmethyl)-7-isobutyl-5-methyl-3-(pyrrolidin-3-ylamino)-2H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

반응 조건

온도
130 °C

실험 절차

2-(biphenyl-4-ylmethyl)-3-chloro-7-isobutyl-5-methyl-2H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione (25 mg, 0.056 mmol) is dissolved in anhydrous and degassed THF, and then (S)-tert-butyl 3-aminopyrrolidine-1-carboxylate (64 mg, 0.34 mmol), Pd2(dba)3 (25 mg, 0.026 mmol) and Xantphos (16 mg, 0.026 mmol) are added, followed by tBuOK (7.5 mg, 0.067 mmol). The reaction mixture is heated in microwave at 130° C. for 2.5 h. After cooling, solvent is removed. The residue is diluted with ethyl acetate (50 mL), and then washed with sodium carbonate aqueous solution three times. Solvent is removed under reduced pressure, the residue is treated with 50% TFA in CH2Cl2 (v/v) at room temperature for 6 hours. Evaporation to remove TFA and solvent, and the residue is purified by a semi-preparative HPLC to give pure product. MS (ESI) m/z 473.2 [M+H]+.

후처리

  1. customdegassed THF
  2. temperatureAfter cooling
  3. customsolvent is removed
  4. additionThe residue is diluted with ethyl acetate (50 mL)
  5. washwashed with sodium carbonate aqueous solution three times
  6. customSolvent is removed under reduced pressure
  7. additionthe residue is treated with 50% TFA in CH2Cl2 (v/v) at room temperature for 6 hours
  8. customEvaporation
  9. customto remove TFA and solvent
  10. customthe residue is purified by a semi-preparative HPLC
  11. customto give pure product

출처 및 근거

ORD 기록
ord-ea4b18044c2a44c29d3eb328e111d7a5
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846693B2

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