Sodium Hydroxide → HCID 178503035, compound

HRID 1525272Notes

Reaction equation

HRID 1525272 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([NH:22][C:23]([C:25]1[C:26]([OH:36])=[N:27][C:28]([N:31]2[CH:35]=[CH:34][CH:33]=[N:32]2)=[N:29][CH:30]=1)=[O:24])[C:10]1[CH:15]=[CH:14][C:13]([P:16]([CH3:21])(=[O:20])[O:17]CC)=[CH:12][CH:11]=1.[OH-].[Na+]>O1CCOCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@H:9]([NH:22][C:23]([C:25]1[C:26]([OH:36])=[N:27][C:28]([N:31]2[CH:35]=[CH:34][CH:33]=[N:32]2)=[N:29][CH:30]=1)=[O:24])[C:10]1[CH:15]=[CH:14][C:13]([P:16]([CH3:21])(=[O:17])[OH:20])=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 178476765HCID 178476765, compound2×

Product 1

HCID 178503035HCID 178503035, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 4-((S)-(2,4-difluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinate, 21-e, (400 mg, 0.78 mmol) was dissolved in 2 ml of dioxane and treated with 0.2 ml of 5N NaOH. The mixture was heated at 80° C. for 30 min. Then the mixture was concentrated under vacuum. The residue was diluted with water and washed with ethyl acetate. The aqueous layer was acidified with AcOH and evaporated to dryness. The residue was used for prep-HPLC to afford the product, 21-1, (250 mg, 66%). 1H NMR (300 MHz, CD3OD): δ 8.67 (s, 1H), 8.58 (s, 1H), 7.92 (s, 1H), 7.81 (m, 2H), 7.48 (m, 3H), 7.01 (m, 2H), 6.66 (s, 1H), 6.60 (s, 1H), 1.67 (d, 3H). (M−H)−=484.0.

Workup

  1. concentrationThen the mixture was concentrated under vacuum
  2. additionThe residue was diluted with water
  3. washwashed with ethyl acetate
  4. customevaporated to dryness
  5. customto afford the product, 21-1, (250 mg, 66%)

Sources & evidence

ORD record
ord-c2d88a26b4794cdf92b16579109ce688
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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