Acetyl chloride → HCID 178502293, compound

HRID 1800787Notes

Reaction equation

HRID 1800787 reaction equation
[CH3:1][CH:2]([CH3:59])[C@H:3]([NH:54][C:55](=[O:58])[O:56][CH3:57])[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]1[NH:12][CH:13]=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4[N:29]=[C:30]([CH:33]5[CH2:37][C:36]6([CH2:42][CH2:41][NH:40][CH2:39][CH2:38]6)[CH2:35][N:34]5[C:43](=[O:53])[C@@H:44]([NH:48][C:49]([O:51][CH3:52])=[O:50])[CH:45]([CH3:47])[CH3:46])[NH:31][CH:32]=4)=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)[N:15]=1)=[O:5].C(N(CC)CC)C.[C:67](Cl)(=[O:69])C.[C:71](=O)([O-])[O-:72].[K+].[K+]>C(Cl)Cl>[CH3:52][O:51][C:49]([NH:48][C@H:44]([C:43]([N:34]1[CH:33]([C:30]2[NH:31][CH:32]=[C:28]([C:25]3[CH:24]=[CH:23][C:22]([C:19]4[CH:20]=[CH:21][C:16]([C:14]5[N:15]=[C:11]([C@@H:7]6[CH2:8][CH2:9][CH2:10][N:6]6[C:4](=[O:5])[C@H:3]([CH:2]([CH3:59])[CH3:1])[NH:54][C:55]([O:56][CH3:57])=[O:58])[NH:12][CH:13]=5)=[CH:17][CH:18]=4)=[CH:27][CH:26]=3)[N:29]=2)[CH2:37][C:36]2([CH2:38][CH2:39][N:40]([C:71]([O:69][CH3:67])=[O:72])[CH2:41][CH2:42]2)[CH2:35]1)=[O:53])[CH:45]([CH3:46])[CH3:47])=[O:50]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 178502291HCID 178502291, compound

Product 1

HCID 178502293HCID 178502293, compoundYield 86.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl [(1S)-2-methyl-1-({(2S)-2-[4-(4′-{2-[2-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}butanoyl)-2,8-diazaspiro[4.5]dec-3-yl]-1H-imidazol-4-yl}-4-biphenylyl)-1H-imidazol-2-yl]-1-pyrrolidinyl}carbonyl)propyl]carbamate (Example 20) (19 mg, 0.02 mmol) in anhydrous CH2Cl2 (0.5 mL) was added triethylamine (0.016 mL, 0.12 mmol) followed by acetyl chloride (0.011 mL, 0.14 mmol) and the reaction stirred at room temperature for 1 h. The reaction is concentrated in vacuo and dissolved in methanol (0.7 mL) to which was added potassium carbonate (30 mg, 0.22 mmol) and the reaction was stirred at room temperature for 2 h. The reaction was concentrated in vacuo and partitioned between CH2Cl2 and water (3 mL each) and the aqueous layer extracted with CH2Cl2 (3 mL) and the organic layers combined and dried (MgSO4) and concentrated in vacuo to afford the title compound as a yellow solid (15 mg, 74% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.51-7.92 (m, 10H) 7.32 (br. s., 2H) 5.02-5.25 (m, 1H) 4.03-4.31 (m, 2H) 3.75-4.05 (m, 2H) 3.61-3.72 (m, 7H) 3.34-3.60 (m, 4H) 1.82-2.50 (m, 7H) 1.70 (br. s., 2H) 1.44-1.63 (m, 4H) 1.27 (br. s., 4H) 0.77-1.10 (m, 14H). HRMS for C46H60N9O8 (M+H)+ calc: 866.4565, found: 850.4564. Purity (LC-MS): 96%.

Workup

  1. concentrationThe reaction is concentrated in vacuo
  2. dissolutiondissolved in methanol (0.7 mL) to which
  3. stirringthe reaction was stirred at room temperature for 2 h
  4. concentrationThe reaction was concentrated in vacuo
  5. custompartitioned between CH2Cl2 and water (3 mL each)
  6. extractionthe aqueous layer extracted with CH2Cl2 (3 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-79005162cfda44d3a095db0c7465c16e
Source dataset
uspto-grants-2013_01
Patent number
US08344155B2

Reaction notes

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