Acetic Anhydride → HCID 136374773, compound

HRID 2110598Notes

Reaction equation

HRID 2110598 reaction equation
[NH2:1][CH2:2][C:3]([NH:5][C:6]1([CH2:35][CH2:36][CH:37]([CH3:39])[CH3:38])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([OH:16])=[C:8]([C:17]2[NH:22][C:21]3[CH:23]=[CH:24][C:25]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[CH:26][C:20]=3[S:19](=[O:33])(=[O:32])[N:18]=2)[C:7]1=[O:34])=[O:4].[C:40](OC(=O)C)(=[O:42])[CH3:41].C(N(CC)CC)C>ClCCl>[C:40]([NH:1][CH2:2][C:3]([NH:5][C:6]1([CH2:35][CH2:36][CH:37]([CH3:39])[CH3:38])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([OH:16])=[C:8]([C:17]2[NH:22][C:21]3[CH:23]=[CH:24][C:25]([NH:27][S:28]([CH3:31])(=[O:29])=[O:30])=[CH:26][C:20]=3[S:19](=[O:32])(=[O:33])[N:18]=2)[C:7]1=[O:34])=[O:4])(=[O:42])[CH3:41]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 136383508HCID 136383508, compound

Product 1

HCID 136374773HCID 136374773, compoundYield 47.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the product of Example 46 (10 mg, 0.017 mmol) in dichloromethane (0.25 mL) was added acetic anhydride (8 μL, 0.087 mmol) followed by addition of triethylamine (7 μL, 0.052 mmol). The reaction mixture was stirred at room temperature for 18 h. The solution was then diluted with dichloromethane (1 mL) and washed with aqueous 1 N HCl (2×0.5 mL), dried (Na2SO4), and concentrated in vacuo. The resulting residue was dissolved in methanol (0.5 mL) and treated with excess K2CO3 for 30 min. The heterogeneous solution was filtered and the filtrate concentrated in vacuo. The residue was then taken up in ethyl acetate (1 mL), washed with aqueous 1 N HCl (2×1 mL), dried (Na2SO4), and concentrated in vacuo. Column chromatography on silica (10% methanol/dichloromethane) afforded the title compound as a light yellow solid (5 mg, 45%). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.61-0.75 (m, 6H), 0.79-0.97 (m, 1H), 1.16-1.35 (m, 2H), 1.56-1.71 (m, 1H), 1.78 (s, 3H), 1.83-1.97 (m, 1H), 2.99 (s, 3H), 3.64-3.88 (m, 2H), 7.26-7.34 (m, 2H), 7.35-7.44 (m, 2H), 7.46 (d, J=2.21 Hz, 1H), 7.91 (t, J=5.52 Hz, 1H), 7.96-8.02 (m, 1H), 8.36 (s, 1H), 9.86 (s, 1H), 15.39 (s, 1H); MS m/z 618.0 (M+H)+.

Workup

  1. washwashed with aqueous 1 N HCl (2×0.5 mL)
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. dissolutionThe resulting residue was dissolved in methanol (0.5 mL)
  5. additiontreated with excess K2CO3 for 30 min
  6. filtrationThe heterogeneous solution was filtered
  7. concentrationthe filtrate concentrated in vacuo
  8. washwashed with aqueous 1 N HCl (2×1 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-206cdb4bf37d4fb0a8457d08bd7247ca
Source dataset
uspto-grants-2009_04
Patent number
US07517876B2

Reaction notes

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