HCID 86693107, compound → HCID 86693106, compound

HRID 575079Notes

Reaction equation

HRID 575079 reaction equation
[OH:1][C:2]1([C:15]#[C:16][C:17]2[C:18]([F:34])=[CH:19][C:20]3[O:29][CH2:28][CH2:27][N:26]4[C:22](=[N:23][C:24]([C:30]([NH2:32])=[O:31])=[CH:25]4)[C:21]=3[CH:33]=2)[CH2:5][CH:4]([O:6]C(=O)C2C=CC=CC=2)[CH2:3]1>CO.ClCCl.O>[OH:1][C:2]1([C:15]#[C:16][C:17]2[C:18]([F:34])=[CH:19][C:20]3[O:29][CH2:28][CH2:27][N:26]4[C:22](=[N:23][C:24]([C:30]([NH2:32])=[O:31])=[CH:25]4)[C:21]=3[CH:33]=2)[CH2:3][CH:4]([OH:6])[CH2:5]1

Participants

5

Reactant 1

HCID 86693107HCID 86693107, compound

Product 1

HCID 86693106HCID 86693106, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

In a 25-mL round-bottom flask, a suspension of 9-(1-hydroxy-3-benzoyloxy-cyclobutylethynyl)-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide (190 mg, ˜0.4 mmol), lithiumol (96 mg, 4.01 mmol) in methanol (0.5 mL) and water (1 mL) was stirred at room temperature overnight. The resulting solution was diluted with 20 mL of dichloromethane and 10 mL water. The organic layer was washed with 10 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with dichloromethane/methanol (1:10). This resulted in 7 mg of 9-(1,3-Dihydroxy-cyclobutylethynyl)-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a light yellow solid (single undetermined diasteromer). LC-MS (ES, m/z):358[M+H]+; 1H-NMR (400 MHz, DMSO-d6, ppm) δ: 8.570 (d, 1H), 7.783 (s, 1H), 7.591 (br s, 1H), 7.139 (br s, 1H), 7.015 (d, 1H), 5.982 (s, 1H), 5.200 (d, 1H), 4.520-4.496 (m, 4H), 4.000-3.949 (m, 1H), 2.760-2.716 (m, 2H), 2.164-2.115 (m, 2H).

Workup

  1. washThe organic layer was washed with 10 mL of brine
  2. dry with materialThe mixture was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under vacuum
  4. customThis resulted in 7 mg of 9-(1,3-Dihydroxy-cyclobutylethynyl)-8-fluoro-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid amide as a light yellow solid (single undetermined diasteromer)

Sources & evidence

ORD record
ord-8f8709c0a6af410a90d60d3c76ea9de5
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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