Benzyl chloroformate → HCID 131718097, compound

HRID 2255543Notes

Reaction equation

HRID 2255543 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([CH2:14][CH2:15][CH2:16][CH3:17])[N:8]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]3[N:35]([C:36]([C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[N:34]=[N:33][N:32]=3)=[CH:21][CH:20]=1)[C:7]2=[O:55].[CH2:56]([O:63][C:64](Cl)=[O:65])[C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1>CN(C=O)C>[CH2:14]([C:9]1[N:8]([CH2:18][C:19]2[CH:20]=[CH:21][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]3[N:35]([C:36]([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=4)([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)[C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=4)[N:34]=[N:33][N:32]=3)=[CH:23][CH:24]=2)[C:7](=[O:55])[C:6]2[C:11](=[CH:12][CH:13]=[C:4]([NH:3][C:64]([O:63][CH2:56][C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=3)=[O:65])[CH:5]=2)[N:10]=1)[CH2:15][CH2:16][CH3:17]

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 24758Sodium hydrideHCID 131718094HCID 131718094, compound

Product 1

HCID 131718097HCID 131718097, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 4 mg (0.12 mmol) of 80% NaH in oil in 1 mL of dry DMF under nitrogen was added at 0° C. a solution of 69 mg (0.1 mmol) of the 6-aminoquinazoline from Example 40. A bright blue solution was formed. After 0.5 hours 18.8 mg (0.1 mmol) of benzylchloroformate was added via syringe. The blue colour rapidly dissipated and the reaction mixture was stirred for 3 hours while allowing the temperature to rise to room temperature. The reaction mixture was concentrated in vacuo and the residue was dissolved in 25 mL of EtOAc and 5 mL of water. The aqueous phase was extracted with EtOAc (2×5 mL) and the combined organic phases were washed with water (1×5 mL) and brine (1×5 mL) and dried over MgSO4. The mixture was filtered and concentrated in vacuo and the residue was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexane to give 51.7 mg (0.62 mmol), 62% yield. 1H-NMR (CDCl3 300 MHz): 0.88 (t, 3H, J=7.3 Hz), 1.32 (m, 2H), 1.68 (m, 2H), 2.60 (3 line m, 2H, J= 8.41 Hz), 5.19 (s, 2H), 5.29 (bs, 2H), 6.90 (m, 8H), 7.09 (d, 1H, J=8.2 Hz), 7.2-7.52 (m, 18H), 7.65 (d, 1H, J=8.8 Hz), 7.91 (m, 1H), 8.19 (m, 2H).

Workup

  1. customA bright blue solution was formed
  2. customto rise to room temperature
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. dissolutionthe residue was dissolved in 25 mL of EtOAc
  5. extractionThe aqueous phase was extracted with EtOAc (2×5 mL)
  6. washthe combined organic phases were washed with water (1×5 mL) and brine (1×5 mL)
  7. dry with materialdried over MgSO4
  8. filtrationThe mixture was filtered
  9. concentrationconcentrated in vacuo
  10. customthe residue was purified by flash chromatography over silica gel eluting with 30% EtOAc/hexane
  11. customto give 51.7 mg (0.62 mmol), 62% yield

Sources & evidence

ORD record
ord-3eff9e30abc642a9b5a7291afe053743
Source dataset
uspto-grants-1993_08
Patent number
US05240928

Reaction notes

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