Trifluoroacetic acid → HCID 54692317, compound

HRID 1162840Notes

Reaction equation

HRID 1162840 reaction equation
Cl.C([O:5][C:6]1[C:11](=[O:12])[N:10]([CH:13]([CH3:15])[CH3:14])[C:9](=[O:16])[N:8]2[CH:17]([CH2:30][CH2:31][NH:32][CH3:33])[CH2:18][N:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[C:20](=[O:21])[C:7]=12)(=O)C.[CH:34]([N:37]=[C:38]=[S:39])([CH3:36])[CH3:35].C([O-])([O-])=O.[K+].[K+].FC(F)(F)C(O)=O>C(Cl)Cl.CCOC(C)=O.CO.C(N(CC)CC)C>[F:29][C:26]1[CH:25]=[CH:24][C:23]([CH2:22][N:19]2[CH2:18][CH:17]([CH2:30][CH2:31][N:32]([CH3:33])[C:38]([NH:37][CH:34]([CH3:36])[CH3:35])=[S:39])[N:8]3[C:9](=[O:16])[N:10]([CH:13]([CH3:14])[CH3:15])[C:11](=[O:12])[C:6]([OH:5])=[C:7]3[C:20]2=[O:21])=[CH:28][CH:27]=1

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 75263Isopropyl IsothiocyanateHCID 68432474HCID 68432474, compound

Product 1

HCID 54692317HCID 54692317, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 2-(4-fluorobenzyl)-7-isopropyl-4-[2-(methylamino)ethyl]-1,6,8-trioxo-1,3,4,6,7,8-hexahydro-2H-pyrazino[1,2-c]pyrimidin-9-yl acetate hydrochloride (37 mg, 0.077 mmol) in CH2Cl2 (830 μL) were added isopropyl isothiocyanate (15 μL) and triethylamine (36 μL) in CH2Cl2 (214 μL). The reaction was stirred at ambient temperature for 18 h. The resulting mixture was diluted with EtOAc and filtered, washing with excess EtOAc. The filtrate was concentrated at 40° C. under a steady stream of nitrogen to afford a sticky solid which was dissolved in MeOH (1.5 mL) and treated with K2CO3 (64 mg, 0.46 mmol). The reaction was stirred at ambient temperature for 18 h. Following addition of trifluoroacetic acid, the mixture was filtered through a cotton plug, purified by reverse phase chromatography [95:5 water (+0.1% TFA)/MeCN (+0.1% TFA) to 5:95 water (+0.1% TFA)/MeCN (+0.1% TFA)], and azeotroped with CH2Cl2 to afford the title compound as an off-white foam. 1H NMR (500 MHz, CDCl3) δ 11.80 (br s, 1H), 7.40-7.37 (m, 2H), 7.08-7.05 (m, 2H), 4.69 (d, J=14.5 Hz, 1H), 4.60-4.52 (m, 2H), 4.32-4.26 (m, 1H), 4.09 (d, J=14.0 Hz, 1H), 3.57 (dd, J=3.5, 14.0 Hz, 1H), 3.51-3.40 (m, 2H), 3.01 (s, 3H), 1.71 (br s, 1H), 1.46 (d, J=7.0 Hz, 6H), 1.26 (dd, J=3.5, 6.5 Hz, 6H). HRMS (FT/ES) M+H: calcd for (C24H32FN5O4S)+ 506.2232. found 506.2247.

Workup

  1. filtrationfiltered
  2. washwashing with excess EtOAc
  3. concentrationThe filtrate was concentrated at 40° C. under a steady stream of nitrogen
  4. customto afford a sticky solid which
  5. stirringThe reaction was stirred at ambient temperature for 18 h
  6. filtrationthe mixture was filtered through a cotton plug
  7. custompurified by reverse phase chromatography [95:5 water (+0.1% TFA)/MeCN (+0.1% TFA) to 5:95 water (+0.1% TFA)/MeCN (+0.1% TFA)]
  8. customazeotroped with CH2Cl2

Sources & evidence

ORD record
ord-a75bcae098f948c6b217df3f6e4e2dd8
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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