Dimethylformamide → N-(4-(methoxymethyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-yl)-N-((S)-2-(4-nitrophenylsulfonamido)-3-(4-(trifluoromethyl)phenyl)propyl)acetamide

HRID 2109704Notes

Reaction equation

HRID 2109704 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[N:5]=[C:6]([NH:18][C:19](=[O:21])[CH3:20])[S:7][C:8]=1[C:9]1[S:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][C:16]=2[N:17]=1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C=O)C.[F:33][C:34]([F:58])([F:57])[C:35]1[CH:56]=[CH:55][C:38]([CH2:39][CH:40]2[CH2:42][N@@:41]2[S:43]([C:46]2[CH:51]=[CH:50][C:49]([N+:52]([O-:54])=[O:53])=[CH:48][CH:47]=2)(=[O:45])=[O:44])=[CH:37][CH:36]=1>C(Cl)Cl.CO>[CH3:1][O:2][CH2:3][C:4]1[N:5]=[C:6]([N:18]([CH2:42][C@@H:40]([NH:41][S:43]([C:46]2[CH:47]=[CH:48][C:49]([N+:52]([O-:54])=[O:53])=[CH:50][CH:51]=2)(=[O:44])=[O:45])[CH2:39][C:38]2[CH:55]=[CH:56][C:35]([C:34]([F:57])([F:33])[F:58])=[CH:36][CH:37]=2)[C:19](=[O:21])[CH3:20])[S:7][C:8]=1[C:9]1[S:10][C:11]2[CH:12]=[N:13][CH:14]=[CH:15][C:16]=2[N:17]=1

Participants

7

Reactant 4

HCID 6228Dimethylformamide2×HCID 10796Cesium carbonateHCID 57633920N-(4-(methoxymethyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-yl)acetamideHCID 178526727HCID 178526727, compound

Product 1

HCID 57931099N-(4-(methoxymethyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-yl)-N-((S)-2-(4-nitrophenylsulfonamido)-3-(4-(trifluoromethyl)phenyl)propyl)acetamideYield 43.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a 50 mL round-bottomed flask was added N-(4-(methoxymethyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-yl)acetamide (0.300 g, 0.936 mmol), Cs2CO3 (0.610 g, 1.87 mmol), and DMF (0.0721 mL, 0.936 mmol). The resulting solution was heated to 50° C. A DMF solution of (S)-2-(4-(trifluoromethyl)benzyl)-1-(4-nitrophenylsulfonyl)aziridine (0.724 g, 1.87 mmol) was added to the reaction dropwise, and the reaction mixture was monitored by LCMS. After approximately 30 minutes, the solvent was removed and the residue was taken up in EtOAc and washed with saturated sodium bicarbonate. The solution was dried over sodium sulfate, filtered and loaded onto a plug of silica gel. Chromatography through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 1% to 10% 2 M NH3.MeOH in DCM, to provide N-(4-(methoxymethyl)-5-(thiazolo[5,4-c]pyridin-2-yl)thiazol-2-yl)-N-((S)-2-(4-nitrophenylsulfonamido)-3-(4-(trifluoromethyl)phenyl)propyl)acetamide (0.290 g, 0.410 mmol, 43.8% yield). LCMS (M+H) 707 calc. for C29H26F3N6O6S3 707.1.

Workup

  1. customthe solvent was removed
  2. washwashed with saturated sodium bicarbonate
  3. dry with materialThe solution was dried over sodium sulfate
  4. filtrationfiltered
  5. washChromatography through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 1% to 10% 2 M NH3

Sources & evidence

ORD record
ord-faeb03a468264f3680cd6ab78801a3be
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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