Ammonium Acetate → HCID 178502359, compound

HRID 1748878Notes

Reaction equation

HRID 1748878 reaction equation
[CH3:1][CH:2]([CH3:60])[C@H:3]([NH:55][C:56](=[O:59])[O:57][CH3:58])[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](=O)[CH2:29][NH:30][C:31]([CH:33]4[CH2:37][CH2:36][C:35]5([CH2:42][CH2:41][O:40][CH2:39][CH2:38]5)[N:34]4[C:43](=[O:53])[C@@H:44]([NH:48][C:49]([O:51][CH3:52])=[O:50])[CH:45]([CH3:47])[CH3:46])=O)=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)[N:15]=1)=[O:5].C([O-])(=O)C.[NH4+:65]>O1CCOCC1>[CH3:60][CH:2]([CH3:1])[C@H:3]([NH:55][C:56](=[O:59])[O:57][CH3:58])[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:17]=[CH:18][C:19]([C:22]3[CH:23]=[CH:24][C:25]([C:28]4[N:65]=[C:31]([CH:33]5[CH2:37][CH2:36][C:35]6([CH2:38][CH2:39][O:40][CH2:41][CH2:42]6)[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:30][CH:29]=4)=[CH:26][CH:27]=3)=[CH:20][CH:21]=2)[N:15]=1)=[O:5]

Participants

4

Reactant 2

HCID 517165Ammonium AcetateHCID 178502366HCID 178502366, compound

Product 1

HCID 178502359HCID 178502359, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of methyl ((1S)-2-methyl-1-{[(2S)-2-(4-{4′-[({[1-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}butanoyl)-8-oxa-1-azaspiro[4.5]dec-2-yl]carbonyl}amino)acetyl]-4-biphenylyl}-1H-imidazol-2-yl)-1-pyrrolidinyl]carbonyl}propyl)carbamate (169) (71 mg, 0.09 mmol) in anhydrous dioxane (1 mL) was added ammonium acetate (66 mg, 0.86 mmol) and the reaction was degassed with nitrogen and heated to 110° C. for 48 h in a sealed tube. The reaction was purified by HPLC eluting with 10-90% water/acetonitrile/0.2% NH4OH to afford the title compound as an off-white solid (10 mg, 14% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.56-7.86 (m, 9H) 7.16-7.44 (m, 2H) 6.88-7.09 (m, 1H) 5.72 (br. s., 1H) 5.09-5.21 (m, 1H) 4.03-4.28 (m, 1H) 3.80-4.04 (m, 6H) 3.42-3.71 (m, 9H) 2.11-2.56 (m, 8H) 1.88-2.11 (m, 6H) 0.80-1.06 (m, 12H). HRMS for C44H57N8O7 (M+H)+ calc: 809.4350. found: 809.4347. Purity (LC-MS): 93%.

Workup

  1. customthe reaction was degassed with nitrogen
  2. customThe reaction was purified by HPLC
  3. washeluting with 10-90% water/acetonitrile/0.2% NH4OH

Sources & evidence

ORD record
ord-23db4c06f02c475a9535ee5dbea4630e
Source dataset
uspto-grants-2015_10
Patent number
US09150587B2

Reaction notes

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