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

HRID 2109720Notes

Reaction equation

HRID 2109720 reaction equation
[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

Participants

7

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-eebd43348ba04881a676e70afaa1bd94
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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