Hydrochloric Acid → HCID 178485855, compound

HRID 409810Notes

Reaction equation

HRID 409810 reaction equation
C(O[C:6]([N:8]([CH3:39])[C@H:9]([CH2:23][O:24][C:25](=[O:38])[NH:26][C:27]1[N:28]=[CH:29][C:30]2[C:35]([CH:36]=1)=[CH:34][C:33]([F:37])=[CH:32][CH:31]=2)[CH2:10][C:11]1[N:12]=[CH:13][N:14](C(OC(C)(C)C)=O)[CH:15]=1)=[O:7])(C)(C)C.Cl.CCN(C(C)C)C(C)C.[Cl:50][C:51]1[C:70]([F:71])=[CH:69][CH:68]=[CH:67][C:52]=1[CH2:53][NH:54]C(=O)OC1C=CC([N+]([O-])=O)=CC=1>C1COCC1>[F:37][C:33]1[CH:32]=[C:31]2[C:30](=[CH:35][CH:34]=1)[CH:29]=[N:28][C:27]([NH:26][C:25](=[O:38])[O:24][CH2:23][C@@H:9]([N:8]([CH3:39])[C:6]([NH:54][CH2:53][C:52]1[CH:67]=[CH:68][CH:69]=[C:70]([F:71])[C:51]=1[Cl:50])=[O:7])[CH2:10][C:11]1[N:12]=[CH:13][NH:14][CH:15]=1)=[CH:36]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 579475384-Nitrophenyl 2-chloro-3-fluorobenzylcarbamateHCID 57947620(S)-tert-butyl 4-(2-(tert-butoxycarbonyl(methyl)amino)-3-(6-fluoroisoquinolin-3-ylcarbamoyloxy)propyl)-1H-imidazole-1-carboxylate

Product 1

HCID 178485855HCID 178485855, compoundYield 13%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-tert-butyl 4-(2-(tert-butoxycarbonyl(methyl)amino)-3-(6-fluoroisoquinolin-3-ylcarbamoyloxy)propyl)-1H-imidazole-1-carboxylate (280 mg, 0.51 mmol) in THF (10 mL) was added HCl (4 N in 1,4-dioxane, 2.55 mL, 10.2 mmol). The reaction mixture was stirred at RT for 1 h and concentrated to dryness. The residue was suspended in THF (20 mL). To the suspension were added DIEA (0.27 mL, 1.53 mmol) and 4-nitrophenyl 2-chloro-3-fluorobenzylcarbamate (166 mg, 0.51 mmol). The reaction mixture was stirred at RT for 2 h and concentrated to dryness. The residue was purified on RP-HPLC using a mixture of acetonitrile and water to give (S)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-3-(1H-imidazol-4-yl)propyl 6-fluoroisoquinolin-3-ylcarbamate (35 mg, 13%). LRMS (M+H+) m/z 529.5.

Workup

  1. concentrationconcentrated to dryness
  2. stirringThe reaction mixture was stirred at RT for 2 h
  3. concentrationconcentrated to dryness
  4. customThe residue was purified on RP-HPLC
  5. additiona mixture of acetonitrile and water

Sources & evidence

ORD record
ord-d36f6208f3d045d980328ba5c1315a54
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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