Hydrochloric Acid → HCID 178508633, compound

HRID 2237625Notes

Reaction equation

HRID 2237625 reaction equation
[NH2:1][C:2]1[C:7]2[C:8](=[O:30])[N:9]([C:13]3[CH:18]=[CH:17][C:16]([C@H:19]4[CH2:24][CH2:23][C@H:22]([CH2:25][C:26]([O:28]C)=[O:27])[CH2:21][CH2:20]4)=[CH:15][CH:14]=3)[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=1.[OH-].[Li+].Cl>O1CCOCC1.O>[NH2:1][C:2]1[C:7]2[C:8](=[O:30])[N:9]([C:13]3[CH:14]=[CH:15][C:16]([C@H:19]4[CH2:20][CH2:21][C@H:22]([CH2:25][C:26]([OH:28])=[O:27])[CH2:23][CH2:24]4)=[CH:17][CH:18]=3)[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 178500652HCID 178500652, compound

Product 1

HCID 178508633HCID 178508633, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A stirred solution of methyl {trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6-(5H)-yl)phenyl]cyclohexyl}acetate (5.05 g, 12.3 mmol), from Example 1, and 1N aqueous lithium hydroxide (36.9 mL) in p-dioxane (96 mL) and water (27 mL) was stirred at 50° C. for one hour. After cooling, the reaction solution was adjusted to pH˜3.5 with 6N aqueous hydrochloric acid and the mixture was concentrated to near dryness. This residue was slurried in water (40 mL) for 1 hour, filtered, the solids washed with water (2×20 mL), ether (3×30 mL) and dried in vacuo to afford the title compound as an off-white solid, 4.58 g. 1H NMR (400 MHz, DMSO-d6): δ 8.12 (s, 1H), 7.58 (br s, 2H) 7.21 (s, 4H), 4.56 (m, 2H), 3.92 (m, 2H), 2.42 (m, 1H), 2.08 (m, 2H), 1.75 (m, 5H), 1.42 (q, 2H), 1.05 (q, 2H). m/z=397.3 (M+1). IC50 19.1 nM (range 5.2-63.6 nM).

Workup

  1. temperatureAfter cooling
  2. concentrationthe mixture was concentrated
  3. filtrationfiltered
  4. washthe solids washed with water (2×20 mL), ether (3×30 mL)
  5. customdried in vacuo

Sources & evidence

ORD record
ord-8d629f8d77f744e0a9e7a586306cd2b3
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

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