Hydrochloric Acid → (R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 3-hydroxycyclobutylmethyl ester

HRID 1907319Notes

Reaction equation

HRID 1907319 reaction equation
O1CCCCC1[O:7][CH:8]1[CH2:11][CH:10]([CH2:12][O:13][C:14]([C@@:16]23[CH2:25][N:24]([S:26]([C:29]4[CH:30]=[N:31][C:32]([N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)=[CH:33][CH:34]=4)(=[O:28])=[O:27])[CH2:23][CH2:22][C:21]2=[CH:20][C:19]2[N:41]([C:44]4[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=4)[N:42]=[CH:43][C:18]=2[CH2:17]3)=[O:15])[CH2:9]1.Cl>O1CCCC1.O1CCOCC1>[OH:7][CH:8]1[CH2:11][CH:10]([CH2:12][O:13][C:14]([C@@:16]23[CH2:25][N:24]([S:26]([C:29]4[CH:30]=[N:31][C:32]([N:35]5[CH2:36][CH2:37][O:38][CH2:39][CH2:40]5)=[CH:33][CH:34]=4)(=[O:27])=[O:28])[CH2:23][CH2:22][C:21]2=[CH:20][C:19]2[N:41]([C:44]4[CH:49]=[CH:48][C:47]([F:50])=[CH:46][CH:45]=4)[N:42]=[CH:43][C:18]=2[CH2:17]3)=[O:15])[CH2:9]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66780176(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 3-(tetrahydropyran-2yloxy)-cyclobutylmethyl ester

Product 1

HCID 68194226(R)-1-(4-Fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 3-hydroxycyclobutylmethyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of (R)-1-(4-fluorophenyl)-6-(6-morpholin-4-yl-pyridine-3-sulfonyl]-1,4,5,6,7,8-hexahydro-1,2,6-triaza-cyclopenta[b]naphthalene-4a-carboxylic acid 3-(tetrahydropyran-2yloxy)-cyclobutylmethyl ester in tetrahydrofuran (0.6 mL) was treated with 4.0 M hydrogen chloride in dioxan (1.0 mL) for 30 minutes. The reaction mixture was evaporated under reduced pressure, the residue dissolved in dichloromethane and the solution washed with 2.0M sodium carbonate solution and brine. The organic extracts were dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by preparative reverse-phase HPLC eluting with a mixture of acetonitrile and water containing 0.1% formic acid (2:3 to 85:15 by volume) to give the title compound as a white solid (0.007 g). 1H NMR (400 MHz, CHCl3-d): δ 8.52 (d, 1H), 7.77 (dd, 1H), 7.40-7.30 (m, 3H), 7.18-7.10 (m, 2H), 6.62 (d, 1H), 6.42 (d, 1H), 4.38-4.30 (m, 2H), 4.11 (dd, 2H), 3.80 (t, 5H), 3.66 (t, 4H), 3.27 (d, 1H), 2.88-2.80 (m, 1H), 2.58 (d, 1H), 2.48-2.34 (m, 4H), 2.18-2.06 (m, 4H).

Workup

  1. customThe reaction mixture was evaporated under reduced pressure
  2. dissolutionthe residue dissolved in dichloromethane
  3. washthe solution washed with 2.0M sodium carbonate solution and brine
  4. dry with materialThe organic extracts were dried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative reverse-phase HPLC
  7. washeluting with a mixture of acetonitrile and water containing 0.1% formic acid (2:3 to 85:15 by volume)

Sources & evidence

ORD record
ord-9fc89b82ac8f489cb08afe1f3e0d41a6
Source dataset
uspto-grants-2013_12
Patent number
US08598154B2

Reaction notes

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