Acetic Anhydride → HCID 90281272, compound

HRID 2170368Notes

Reaction equation

HRID 2170368 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:37]2[CH:38]=[CH:39][CH:40]=[C:41]3[C:45]=2[N:44]([CH3:46])[N:43]=[C:42]3[NH:47][S:48]([CH3:51])(=[O:50])=[O:49])[C:5]([C@@H:8]([NH:18][C:19](=[O:36])[CH2:20][N:21]2[C:25]3[C:26]([F:31])([F:30])[C@@H:27]4[CH2:29][C@@H:28]4[C:24]=3[C:23]([C:32]([F:35])([F:34])[F:33])=[N:22]2)[CH2:9][C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=2)=[N:6][CH:7]=1.[C:52](OC(=O)C)(=[O:54])[CH3:53].C(N(CC)CC)C>C(Cl)Cl>[NH2:1][C:2]1[CH:3]=[C:4]([C:37]2[CH:38]=[CH:39][CH:40]=[C:41]3[C:45]=2[N:44]([CH3:46])[N:43]=[C:42]3[N:47]([S:48]([CH3:51])(=[O:49])=[O:50])[C:52](=[O:54])[CH3:53])[C:5]([C@@H:8]([NH:18][C:19](=[O:36])[CH2:20][N:21]2[C:25]3[C:26]([F:30])([F:31])[C@@H:27]4[CH2:29][C@@H:28]4[C:24]=3[C:23]([C:32]([F:35])([F:33])[F:34])=[N:22]2)[CH2:9][C:10]2[CH:11]=[C:12]([F:17])[CH:13]=[C:14]([F:16])[CH:15]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 90281176HCID 90281176, compound

Product 1

HCID 90281272HCID 90281272, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of Compound 35 (20 mg, 0.027 mmol) in methylene chloride (2 mL) was added acetic anhydride (0.03 mL, 0.27 mmol), triethylamine (0.04 mL, 0.027 mmol), and the reaction mixture was stirred for one hour at room temperature. The solution was partitioned between EtOAc and saturated aqueous sodium bicarbonate. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase HPLC eluting with acetonitrile and water (with 0.1% TFA) to afford the title compound 38A: 1H NMR (400 MHz, methanol-d4) δ 8.26 (d, 1H), 7.72 (dd, 1H), 7.18 (m, 1H), 7.09 (d, 1H), 6.76 (tt, 1H), 6.46 (d, 1H), 6.42-6.21 (m, 2H), 4.85-4.52 (m, 3H), 3.50 (m, 6H), 3.12 (m, 1H), 3.00-2.80 (m, 1H), 2.59-2.31 (m, 2H), 1.86 (s, 3H), 1.41 (m, 1H), 1.04 (m, 1H). MS (m/z): 778.95 [M+H]+ and 11 mg of compound 38B. MS (m/z) 820.83 [M+H]+.

Workup

  1. customThe solution was partitioned between EtOAc and saturated aqueous sodium bicarbonate
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase HPLC
  6. washeluting with acetonitrile and water (with 0.1% TFA)

Sources & evidence

ORD record
ord-24053f5405144a9fb3eb653f57af39e0
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

Loading…