Trifluoroacetic acid → 5-amino-2-[2-(4-fluorophenyl)ethyl]-7-(1-(4-chlorophenoxyacetyl)pyrrolidin-3-(S)-ylamino)-thiazolo[5,4-d]pyrimidine

HRID 1507809노트

반응식

HRID 1507809 반응식
[NH2:1][C:2]1[N:3]=[C:4]([NH:20][C@H:21]2[CH2:25][CH2:24][N:23]([C:26](OC(C)(C)C)=[O:27])[CH2:22]2)[C:5]2[N:10]=[C:9]([CH2:11][CH2:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[S:8][C:6]=2[N:7]=1.FC(F)(F)C(O)=O.C(N(C(C)C)CC)(C)C.[Cl:49][C:50]1[CH:60]=[CH:59][C:53]([O:54][CH2:55]C(Cl)=O)=[CH:52][CH:51]=1>ClCCl>[NH2:1][C:2]1[N:3]=[C:4]([NH:20][C@H:21]2[CH2:25][CH2:24][N:23]([C:26](=[O:27])[CH2:55][O:54][C:53]3[CH:59]=[CH:60][C:50]([Cl:49])=[CH:51][CH:52]=3)[CH2:22]2)[C:5]2[N:10]=[C:9]([CH2:11][CH2:12][C:13]3[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=3)[S:8][C:6]=2[N:7]=1

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 77771p-Chlorophenoxyacetyl chlorideHCID 81531DiisopropylethylamineHCID 469168485-amino-2-[2-(4-fluorophenyl)ethyl]-7-(1-tert-butoxycarbonyl-pyrrolidin-3-(S)-ylamino)-thiazolo[5,4-d]pyrimidine

생성물 1

HCID 469168495-amino-2-[2-(4-fluorophenyl)ethyl]-7-(1-(4-chlorophenoxyacetyl)pyrrolidin-3-(S)-ylamino)-thiazolo[5,4-d]pyrimidine수율 46.8%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 5-amino-2-[2-(4-fluorophenyl)ethyl]-7-(1-tert-butoxycarbonyl-pyrrolidin-3-(S)-ylamino)-thiazolo[5,4-d]pyrimidine (70 mg, 0.15 mmol) in dichloromethane (1 ml) was added trifluoroacetic acid (1 ml). The reaction mixture was stirred at room temperature for 2 hours after which the solvents were removed in vacuo. The residue was dissolved in dichloromethane (3 ml) and diisopropylethylamine (1.5 mmol, 252 μL) and 4-chlorophenoxyacetyl chloride (0.17 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours whereupon the solvent was removed in vacuo. The resulting residue was purified by flash chromatography on silica, the mobile phase being a mixture of methanol and dichloromethane (in a ratio gradually ranging from 100% CH2Cl2 to 1.5% CH3OH in CH2Cl2), yielding the pure title compound (37 mg) which was characterized by its mass spectrum: MS m/z (%): 527 ([M+H]+, 100).

후처리

  1. customwere removed in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane (3 ml)
  3. stirringThe reaction mixture was stirred at room temperature for 16 hours whereupon the solvent
  4. customwas removed in vacuo
  5. customThe resulting residue was purified by flash chromatography on silica
  6. additiona mixture of methanol and dichloromethane (in a ratio

출처 및 근거

ORD 기록
ord-80871a9ee02f48b0950486f355c1e97e
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221822B2

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