Cesium carbonate → N-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(phthalazin-6-yl)thiazol-2-amine

HRID 661047노트

반응식

HRID 661047 반응식
[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[S:15][C:14]([NH:16][C:17](=O)OC(C)(C)C)=[N:13][CH:12]=3)=[CH:8][CH:9]=2)[CH:4]=[N:3][N:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].[F:30][C:31]([F:55])([F:54])[C:32]1[CH:53]=[CH:52][C:35]([CH2:36][CH:37]2C[N:38]2S(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)=[CH:34][CH:33]=1.C([O-])([O-])=O.[K+].[K+].SC(O)C>CN(C=O)C>[NH2:38][C@@H:37]([CH2:36][C:35]1[CH:34]=[CH:33][C:32]([C:31]([F:30])([F:54])[F:55])=[CH:53][CH:52]=1)[CH2:17][NH:16][C:14]1[S:15][C:11]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[CH:1]=[N:2][N:3]=[CH:4]3)=[CH:12][N:13]=1

참가 물질

7

반응물 5

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 4713212Mercapto-ethanolHCID 57633940Tert-butyl 5-(phthalazin-6-yl)thiazol-2-ylcarbamateHCID 765713024-(Trifluoromethyl)benzyl-1-(4-nitrophenylsulfonyl)aziridine

생성물 1

HCID 23654432N-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(phthalazin-6-yl)thiazol-2-amine수율 19%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

A solution of tert-butyl 5-(phthalazin-6-yl)thiazol-2-ylcarbamate (0.320 g, 0.97 mmol) and Cs2CO3 (0.63 g, 1.9 mmol) in DMF was stirred at room temperature for 30 minutes. The resulting solution was treated dropwise with ((S)-2-(4-(trifluoromethyl)benzyl-1-(4-nitrophenylsulfonyl)aziridine in DMF, and was then stirred for 30 minutes. The reaction was treated in portions with K2CO3 (0.67 g, 4.9 mmol) and mercaptoethanol (0.23 g, 2.9 mmol) and stirred for 15 minutes. After removing the solvent under reduced pressure, the residue was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 5% to 95% MeOH in DCM. The resulting residue was dissolved in DCM and treated with TFA to provide the title compound (0.100 g, 19% yield). LCMS (M+H) 430.6 calc. for C21H18F3N5S 430.6; 1H NMR (400 MHz, CDCl3-d) δ ppm 9.48 (s, 1H), 9.44 (s, 1H), 8.01 (d, 1H), 7.92 (d, 1H), 7.75 (s, 1H), 7.62 (sd, 3H), 7.35 (d, 2H), 3.92 (dd, 2H), 3.55 (dd, 1H), 3.25 (tt, 1H) 2.98 (dd, 1H), 2.89 (t, 2H), 2.72 (b, 1H).

후처리

  1. stirringstirred for 15 minutes
  2. customAfter removing the solvent under reduced pressure
  3. customchromatographed through a Redi-Sep pre-packed silica gel column (40 g)
  4. washeluting with a gradient of 5% to 95% MeOH in DCM
  5. dissolutionThe resulting residue was dissolved in DCM
  6. additiontreated with TFA

출처 및 근거

ORD 기록
ord-31cb8bec8c544b7bae8de8f7283acf55
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084479B2

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