Potassium Carbonate → HCID 178485813, compound

HRID 1748874Notes

Reaction equation

HRID 1748874 reaction equation
[CH3:1][CH:2]([CH3:57])[C@H:3]([NH:52][C:53](=[O:56])[O:54][CH3:55])[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[CH2:40][C:36]6([CH2:39][NH:38][CH2:37]6)[CH2:35][N:34]5[C:41](=[O:51])[C@@H:42]([NH:46][C:47]([O:49][CH3:50])=[O:48])[CH:43]([CH3:45])[CH3:44])[NH:31][CH:32]=4)=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)[N:15]=1)=[O:5].[CH3:58][N:59]=[C:60]=[O:61].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[CH3:1][CH:2]([CH3:57])[C@H:3]([NH:52][C:53](=[O:56])[O:54][CH3:55])[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:23]=[CH:24][C:25]([C:28]4[N:29]=[C:30]([CH:33]5[CH2:40][C:36]6([CH2:37][N:38]([C:60]([NH:59][CH3:58])=[O:61])[CH2:39]6)[CH2:35][N:34]5[C:41](=[O:51])[C@@H:42]([NH:46][C:47]([O:49][CH3:50])=[O:48])[CH:43]([CH3:44])[CH3:45])[NH:31][CH:32]=4)=[CH:26][CH:27]=3)=[CH:18][CH:17]=2)[N:15]=1)=[O:5]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 12228Methyl IsocyanateHCID 178502299methyl N-[(1S)-1-[(2S)-2-[5-[4-[4-[2-[7-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-2,7-diazaspiro[3.4]octan-6-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate

Product 1

HCID 178485813HCID 178485813, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl [(1S)-2-methyl-1-({(2S)-2-[4-(4′-{2-[6-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}butanoyl)-2,6-diazaspiro[3.4]oct-7-yl]-1H-imidazol-4-yl}-4-biphenylyl)-1H-imidazol-2-yl]-1-pyrrolidinyl}carbonyl)propyl]carbamate (Example 24) (45 mg, 0.06 mmol) in anhydrous CH2Cl2 (0.6 mL) was added methyl isocyanate (0.01 mL, 0.17 mmol) and the reaction stirred at room temperature for 2 h. The solvent was removed in vacuo and the residue dissolved in methanol (1 mL) and potassium carbonate (40 mg, 0.29 mmol) was added and the reaction stirred at room temperature for 18 h. The reaction was partitioned between CH2Cl2 (10 mL) and water (5 mL), the aqueous layer was extracted with CH2Cl2 (5 mL), the organic layers were combined and dried (MgSO4) and concentrated in vacuo to afford the title compound as a yellow solid (34 mg, 70% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.64 (br. s., 10H) 7.33 (br. s., 2H) 5.06-5.22 (m, 1H) 4.03-4.46 (m, 3H) 3.73-4.04 (m, 8H) 3.54-3.73 (m, 6H) 3.46 (q, J=7.0 Hz, 2H) 2.52-2.76 (m, 5H) 2.10-2.53 (m, 4H) 2.02 (br. s., 3H) 0.70-1.09 (m, 12H). HRMS for C44H57N10O7 (M+H)+ calc: 837.4412. found: 838.4416. Purity (LC-MS): 91%.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in methanol (1 mL)
  3. stirringthe reaction stirred at room temperature for 18 h
  4. customThe reaction was partitioned between CH2Cl2 (10 mL) and water (5 mL)
  5. extractionthe aqueous layer was extracted with CH2Cl2 (5 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bfb1dd885e5d40e796f7106b271b0992
Source dataset
uspto-grants-2015_10
Patent number
US09150587B2

Reaction notes

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