Ammonia → (9-(3-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 1689299Notes

Reaction equation

HRID 1689299 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31]([CH2:33][CH2:34][OH:35])[CH:32]=1)[CH2:5][N:6]1[CH2:29][CH2:28][C:9]2([O:14][CH2:13][CH2:12][N:11]([C:15]([C:17]3[N:18]=[C:19]([C:22]4[CH:27]=CC=C[CH:23]=4)[S:20][CH:21]=3)=[O:16])[CH2:10]2)[CH2:8][CH2:7]1.N>CO>[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[C:31]([CH2:33][CH2:34][OH:35])[CH:32]=1)[CH2:5][N:6]1[CH2:29][CH2:28][C:9]2([O:14][CH2:13][CH2:12][N:11]([C:15]([C:17]3[N:18]=[C:19]([CH:22]([CH3:27])[CH3:23])[S:20][CH:21]=3)=[O:16])[CH2:10]2)[CH2:8][CH2:7]1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 57989277(9-(3-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-phenylthiazol-4-yl)methanone

Product 1

HCID 57989004(9-(3-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 2,2,2-trifluoro-1-(9-(3-fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone (example 41, step d) (0.21 g) in methanol (3 mL) was added to ammonia (35% aqueous solution, 15 mL) and the reaction mixture stirred at 20° C. for 1 hour. The mixture was evaporated to dryness under reduced pressure and the residue azeotroped three times with acetonitrile. The residue was dissolved in DMF (7 mL) and treated with 2-isopropylthiazole-4-carboxylic acid (0.098 g) followed by triethylamine (0.290 mL) and then HATU (0.257 g) and the resultant mixture stirred at 20° C. for 1 hour. The mixture was partitioned between ethyl acetate and brine, the organic layer was washed twice with brine, dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure to afford the subtitled compound. Yield 0.25 g.

Workup

  1. customThe mixture was evaporated to dryness under reduced pressure
  2. customthe residue azeotroped three times with acetonitrile
  3. dissolutionThe residue was dissolved in DMF (7 mL)
  4. additiontreated with 2-isopropylthiazole-4-carboxylic acid (0.098 g)
  5. stirringHATU (0.257 g) and the resultant mixture stirred at 20° C. for 1 hour
  6. customThe mixture was partitioned between ethyl acetate and brine
  7. washthe organic layer was washed twice with brine
  8. dry with materialdried over sodium sulphate
  9. filtrationfiltered
  10. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-986f671ef1a54087a078e2935d27261e
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

Loading…