Hydrochloric Acid → HCID 54692319, compound

HRID 1162841Notes

Reaction equation

HRID 1162841 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.[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(N(CC)CC)C.C[O-].[Na+].Cl.FC(F)(F)C(O)=O>C(Cl)Cl.CN(C)C1C=CN=CC=1.CCOC(C)=O.CO>[F:29][C:26]1[CH:27]=[CH:28][C:23]([CH2:22][N:19]2[CH2:18][CH:17]([CH2:30][CH2:31][N:32]([CH3:33])[C:34](=[O:41])[C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[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:24][CH:25]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 10942334Sodium MethoxideHCID 68432474HCID 68432474, compound

Product 1

HCID 54692319HCID 54692319, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

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 (from Example 67, Step 2, 37 mg, 0.077 mmol) was suspended in CH2Cl2 and treated with benzoyl chloride (15 μL, 0.13 mmol), triethylamine (36 μL, 0.26 mmol) in CH2Cl2 (214 μL), and 4-dimethylaminopyridine (2.0 mg, 0.015 mmol) in CH2Cl2 (50 μL). The solution was stirred at ambient temperature for 18 h. The resulting material was suspended in EtOAc and filtered, washing with excess EtOAc. The filtrate was concentrated at 40° C. under a steady stream of nitrogen to yield a sticky solid which was dissolved in MeOH and treated with sodium methoxide in MeOH (25 wt %, 1.5 mL). The reaction was stirred for 30 min at ambient temperature and was then treated with aqueous HCl (1 M) and trifluoroacetic acid. The mixture was concentrated at 40° C. under a steady stream of nitrogen. The resulting residue was taken up in CH2Cl2, filtered, and concentrated. Purification of the remaining residue (dissolved in MeOH) 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)] afforded the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ 11.77 (br s, 1H), 7.47-7.30 (m, 5H), 7.29-7.22 (m, 3H), 4.41 (d, J=14.0 Hz, 1H), 3.93 (d, J=14.0 Hz, 1H), 3.77-3.73 (m, 1H), 3.65 (d, J=11.0 Hz, 1H), 2.98 (s, 3H), 2.77 (d, J=13.0 Hz, 1H), 1.87 (br s, 1H), 1.48 (d, J=6.0 Hz, 6H). HRMS (FT/ES) M+H: calcd for (C27H29FN4O5)+ 509.2195. found 509.2214.

Workup

  1. filtrationfiltered
  2. washwashing with excess EtOAc
  3. concentrationThe filtrate was concentrated at 40° C. under a steady stream of nitrogen
  4. customto yield a sticky solid which
  5. stirringThe reaction was stirred for 30 min at ambient temperature
  6. concentrationThe mixture was concentrated at 40° C. under a steady stream of nitrogen
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification of the remaining residue (dissolved in MeOH) 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)]

Sources & evidence

ORD record
ord-07d87bef11ab48e6abe23140ea72920f
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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