Sulfuric Acid → HCID 69593511, compound

HRID 1246827Notes

Reaction equation

HRID 1246827 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:23])=[N:15][C:14]3[C:9]2=[N:10][CH:11]=[N:12][C:13]=3[N:24]2[CH2:29][CH:28]3[CH:26]([C:27]3([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[C:30]#[N:31])[CH2:25]2)=[CH:4][CH:3]=1.[OH:38]S(O)(=O)=O>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[Cl:23])=[N:15][C:14]3[C:9]2=[N:10][CH:11]=[N:12][C:13]=3[N:24]2[CH2:25][CH:26]3[CH:28]([C:27]3([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[C:30]([NH2:31])=[O:38])[CH2:29]2)=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 86592223HCID 86592223, compound

Product 1

HCID 69593511HCID 69593511, compound

Procedure

A mixture of 3-[9-(4-chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-6-morpholin-4-yl-3-azabicyclo[3.1.0]hexane-6-carbonitrile 29A-8 (28 mg, 0.052 mmol) in concentrated H2SO4 (0.6 ml) was heated at 200° C. for two hours. After the reaction mixture was allowed to cool to room temperature and stir overnight, it was cooled in an ice bath and then carefully quenched with 5 M aqueous NaOH to pH 11. The mixture was extracted with ethyl acetate and then the combined organic layers were washed with brine, dried (MgSO4) and concentrated, in vacuo. The residue was purified on a Biotage™ Flash 12S column using 0–6% methanol in methylene chloride as eluant to give, after trituration from methylene chloride/hexanes, title compound 30A-1 (24 mg, 83%): +ESI MS (M+1) 550.4; 1H NMR (400 MHz, CD2Cl2) δ 8.27 (s, 1H), 7.52–7.49 (m, 1H), 7.44–7.32 (m, 5H), 7.20 (d, J=8.7 Hz, 2H), 5.54 (s, 1H), 5.47 (s, 1H), 5.03 (d, J=12.0 Hz, 1H), 4.37 (d, J=12.0 Hz, 1H), 3.97 (br d, J=9.1 Hz, 1H), 3.68–3.55 (m, 5H), 2.73–2.63 (m, 4H), 2.01 (br s, 1H), 1.96 (br s, 1H).

Workup

  1. temperatureit was cooled in an ice bath
  2. customcarefully quenched with 5 M aqueous NaOH to pH 11
  3. extractionThe mixture was extracted with ethyl acetate
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated, in vacuo
  7. customThe residue was purified on a Biotage™ Flash 12S column
  8. customto give

Sources & evidence

ORD record
ord-a9e33283a03c4850b04ba03414bb69d0
Source dataset
uspto-grants-2006_10
Patent number
US07129239B2

Reaction notes

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