Hydrochloric Acid → 7-[4-(3-Amino-oxetan-3-yl)-phenyl]-8-phenyl-2H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalene-3,6-dione

HRID 1037327Notes

Reaction equation

HRID 1037327 reaction equation
[O:1]=[C:2]1[N:6]2[CH:7]=[CH:8][C:9]3[C:10](=[O:38])[C:11]([C:21]4[CH:26]=[CH:25][C:24]([C:27]5([NH:31]S(C(C)(C)C)=O)[CH2:30][O:29][CH2:28]5)=[CH:23][CH:22]=4)=[C:12]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[O:13][C:14]=3[C:5]2=[N:4][N:3]1COCC[Si](C)(C)C.Cl.O1CCOCC1>CO>[NH2:31][C:27]1([C:24]2[CH:25]=[CH:26][C:21]([C:11]3[C:10](=[O:38])[C:9]4[CH:8]=[CH:7][N:6]5[C:2](=[O:1])[NH:3][N:4]=[C:5]5[C:14]=4[O:13][C:12]=3[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[CH:22][CH:23]=2)[CH2:30][O:29][CH2:28]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86671050HCID 86671050, compound

Product 1

HCID 510300457-[4-(3-Amino-oxetan-3-yl)-phenyl]-8-phenyl-2H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalene-3,6-dioneYield 52%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 2-methyl-propane-2-sulfinic acid (3-{-4-[3,6-dioxo-8-phenyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,6-dihydro-3H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalen-7-yl]-phenyl}-oxetan-3-yl)-amide (46 mg, 0.07 mmol) in MeOH (6 mL) was added a solution of HCl in dioxane (4 M, 0.14 mL, 0.56 mmol) at RT. After 1 h, the reaction mixture was evaporated to dryness. The residue was suspended in DCM (5 mL), cooled in an ice bath, and TFA (1 mL) was added. The mixture was stirred at RT for 1 h before evaporating to dryness. The residue was dissolved in MeOH and loaded on to a 2 g SCX-2 cartridge. The cartridge was washed with MeOH before eluting with 2 M NH3 in MeOH solution. The eluent was collected and evaporated. The resulting residue was subjected to flash chromatography (SiO2, gradient 10 to 30% 2 M NH3/MeOH in DCM) to afford the title compound (15 mg, 52%) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 7.81 (d, J=7.2 Hz, 1H), 7.54 (d, J=8.3 Hz, 2H), 7.44-7.36 (m, 5H), 7.22 (d, J=8.2 Hz, 2H), 6.97 (d, J=7.2 Hz, 1H), 4.70 (d, J=6.1 Hz, 2H), 4.66 (d, J=6.1 Hz, 2H). LCMS (Method E): RT=2.35 min, [M+H]+=427.

Workup

  1. customthe reaction mixture was evaporated to dryness
  2. temperaturecooled in an ice bath
  3. additionTFA (1 mL) was added
  4. custombefore evaporating to dryness
  5. dissolutionThe residue was dissolved in MeOH
  6. washThe cartridge was washed with MeOH
  7. washbefore eluting with 2 M NH3 in MeOH solution
  8. customThe eluent was collected
  9. customevaporated

Sources & evidence

ORD record
ord-8d91f066e6994d13b2416d137440425b
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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