Methanol → HCID 57634033, compound

HRID 2109752Notes

Reaction equation

HRID 2109752 reaction equation
C(OC(=O)[NH:7][C@@H:8]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=1)[CH2:9][N:10]([C:18]1[S:19][C:20]([C:25]2[CH:26]=[C:27]3[C:32](=[CH:33][CH:34]=2)[CH:31]=[N:30][CH:29]=[CH:28]3)=[C:21](C=O)[N:22]=1)C(OC(C)(C)C)=O)(C)(C)C.S1C=[C:50]([CH:52]=[O:53])[N:49]=[CH:48]1.CO.C[O-].[Na+].C1(C)C=CC(S(C[N+]#[C-])(=O)=O)=CC=1.C(Cl)Cl.C(O)(C(F)(F)F)=O>C([SiH](CC)CC)C.C1(C)C=CC=CC=1>[NH2:7][C@@H:8]([CH2:35][C:36]1[CH:41]=[CH:40][C:39]([C:42]([F:44])([F:43])[F:45])=[CH:38][CH:37]=1)[CH2:9][NH:10][C:18]1[S:19][C:20]([C:25]2[CH:34]=[C:33]3[C:32](=[CH:27][CH:26]=2)[CH:31]=[N:30][CH:29]=[CH:28]3)=[C:21]([C:52]2[O:53][CH:48]=[N:49][CH:50]=2)[N:22]=1

Participants

9

Reactant 6

HCID 887MethanolHCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 161915Tosylmethyl isocyanideHCID 10942334Sodium MethoxideHCID 86613772HCID 86613772, compound

Product 1

HCID 57634033HCID 57634033, compoundYield 101%

Reagents, catalysts & solvents 2

HCID 12052TriethylsilaneCatalystHCID 1140TolueneSolvent

Procedure

To a 100 mL round-bottomed flask was added thiazole 4-carboxaldehyde tert-butyl (S)-1-(4-formyl-5-(isoquinolin-6-yl)thiazol-2-yl-(Boc)amino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.098 g, 0.15 mmol), MeOH (0.0060 mL, 0.15 mmol), sodium methoxide (0.027 g, 0.51 mmol) and p-toluenesulfonylmethylisonitrile (0.035 g, 0.18 mmol). The resulting solution was stirred at reflux for about 1 hour until LCMS indicated that the reaction was complete. LCMS indicated complete conversion with removal of one of the Boc groups. The crude reaction was quenched with water and extracted three times with EtOAc. The combined organic layers were dried over sodium sulfate, filtered, and the solvent was removed. The crude product was used immediately in the next step. To a 100 mL round-bottomed flask was added the crude material from the previous step (0.100 g, 0.14 mmol), DCM (0.0092 mL, 0.14 mmol), TFA (0.011 mL, 0.14 mmol), and a few drops of triethylsilane. The reaction was stirred at room temperature and followed by LCMS. Toluene was added, and the solvent was removed. The residue was dissolved in 2 N ammonia in MeOH, and the crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with a gradient of 1% to 10% MeOH in DCM, to provide N-((S)-2-amino-3-(4-(trifluoromethyl)phenyl)propyl)-5-(isoquinolin-6-yl)-4-(oxazol-5-yl)thiazol-2-amine (0.072 g, 101% yield).

Workup

  1. temperatureat reflux for about 1 hour until LCMS
  2. customwith removal of one of the Boc groups
  3. customThe crude reaction
  4. customwas quenched with water
  5. extractionextracted three times with EtOAc
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed
  9. stirringThe reaction was stirred at room temperature
  10. customthe solvent was removed
  11. dissolutionThe residue was dissolved in 2 N ammonia in MeOH
  12. customchromatographed through a Redi-Sep® pre-packed silica gel column (12 g)
  13. washeluting with a gradient of 1% to 10% MeOH in DCM

Sources & evidence

ORD record
ord-b0143323f3ed4daab866e4c3ae9f6513
Source dataset
uspto-grants-2009_04
Patent number
US07514566B2

Reaction notes

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