Hydrochloric Acid → HCID 178502497, compound

HRID 590680Notes

Reaction equation

HRID 590680 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:61]1([CH3:67])[CH2:66][CH2:65][O:64][CH2:63][CH2:62]1)[C:10]([N:12]1[C@@H:16]([CH3:17])[CH2:15][CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[C:23]3[C:28]([CH:29]=[CH:30][C:20]=2[N:19]=1)=[CH:27][C:26]1[C:31]2[C:36]([CH2:37][O:38][C:25]=1[CH:24]=3)=[CH:35][C:34]([C:39]1[NH:43][C:42]([C@@H:44]3[CH2:48][CH2:47][C@H:46]([CH3:49])[N:45]3[C:50](=[O:60])[C@@H:51]([NH:55][C:56](=[O:59])[O:57][CH3:58])[CH:52]([CH3:54])[CH3:53])=[N:41][CH:40]=1)=[CH:33][CH:32]=2)=[O:11])=[O:7])(C)(C)C.Cl.ClC(OC)=O.C(N(C(C)C)CC)(C)C>ClCCl.CO>[CH3:1][O:5][C:6]([NH:8][C@@H:9]([C:61]1([CH3:67])[CH2:62][CH2:63][O:64][CH2:65][CH2:66]1)[C:10]([N:12]1[C@@H:16]([CH3:17])[CH2:15][CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[C:23]3[C:28]([CH:29]=[CH:30][C:20]=2[N:19]=1)=[CH:27][C:26]1[C:31]2[C:36]([CH2:37][O:38][C:25]=1[CH:24]=3)=[CH:35][C:34]([C:39]1[NH:43][C:42]([C@@H:44]3[CH2:48][CH2:47][C@H:46]([CH3:49])[N:45]3[C:50](=[O:60])[C@@H:51]([NH:55][C:56](=[O:59])[O:57][CH3:58])[CH:52]([CH3:54])[CH3:53])=[N:41][CH:40]=1)=[CH:33][CH:32]=2)=[O:11])=[O:7]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 178502498HCID 178502498, compound

Product 1

HCID 178502497HCID 178502497, compoundYield 10.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To as solution of methyl [(2S)-1-{(2S,5S)-2-[5-(2-{(2S,5S)-1-[(2S)-2-[(tert-butoxycarbonyl)amino]-2-(4-methyltetrahydro-2H-pyran-4-yl)acetyl]-5-methylpyrrolidin-2-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-5-methylpyrrolidin-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate (0.594 g, 0.648 mmol) in a mixture of dichloromethane (6.4 mL) and methanol (1.2 mL) was added HCl (4M in dioxanes, 2.4 mL, 9.72 mmol). The solution was heated to 40° C. for 1 h and cooled to room temperature. The solution was then concentrated in vacuo. The resulting solid was dissolved in DMF (3 mL), followed by the addition of methyl chloroformate (0.050 mL, 0.648 mmol) and diisopropylethylamine (0.14 mL, 0.78 mmol). The reaction mixture was stirred at room temperature for 30 minutes. Upon completion by LCMS monitoring, the solution was purified by reverse phase HPLC (Gemini column, 10-45% MeCN/H2O/0.1% TFA). The desired fractions were lyophilized to give methyl [(2S)-1-{(2S,5S)-2-[5-(2-{(2S,5S)-1-[(2S)-2-[(methoxycarbonyl)amino]-2-(4-methyltetrahydro-2H-pyran-4-yl)acetyl]-5-methylpyrrolidin-2-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-5-methylpyrrolidin-1-yl}-3-methyl-1-oxobutan-2-yl]carbamate (0.057 g, 10%). 1H NMR (400 MHz, Methanol-d4) δ 8.63 (s, 1H), 8.19 (d, 1H), 8.09-7.75 (m, 4H), 7.75-7.61 (m, 2H), 7.46-7.24 (m, 1H), 5.39-5.24 (m, 2H), 5.23-5.12 (m, 1H), 4.84-4.60 (m, 2H), 4.44-4.22 (m, 1H), 4.22-4.02 (m, 1H), 3.85-3.62 (m, 8H), 3.60-3.45 (m, 2H), 2.84-2.44 (m, 2H), 2.42-2.23 (m, 3H), 2.12-1.82 (m, 3H), 1.67 (d, 2H), 1.56 (d, 4H), 1.37-1.19 (m, 4H), 1.17-1.03 (m, 4H), 0.98 (d, 3H), 0.88 (d, 3H). MS (ESI) m/z 875.53 [M+H]+.

Workup

  1. temperaturecooled to room temperature
  2. concentrationThe solution was then concentrated in vacuo
  3. dissolutionThe resulting solid was dissolved in DMF (3 mL)
  4. customUpon completion by LCMS monitoring, the solution was purified by reverse phase HPLC (Gemini column, 10-45% MeCN/H2O/0.1% TFA)

Sources & evidence

ORD record
ord-b4af5479b18c4dbb8e71aeba744eb7c5
Source dataset
uspto-grants-2016_01
Patent number
US09233974B2

Reaction notes

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