Sodium Hydroxide → HCID 178503034, compound

HRID 1525267Notes

Reaction equation

HRID 1525267 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 178476764HCID 178476764, compound2×

Product 1

HCID 178503034HCID 178503034, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 4-((R)-(2,4-difluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinate, 20-f, (400 mg, 0.78 mmol) was dissolved in 5 ml of dioxane and treated with 0.5 ml of 5N NaOH. The mixture was heated at 80° C. for one hour. The mixture was then concentrated under vacuum and 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, 20-1, (100 mg, 26%). 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), 7.04 (m, 2H), 6.66 (s, 1H), 6.60 (s, 1H), 1.66 (d, 3H). (M−H)−=484.0.

Workup

  1. concentrationThe mixture was then concentrated under vacuum
  2. additionthe residue was diluted with water
  3. washwashed with ethyl acetate
  4. customevaporated to dryness
  5. customto afford the product, 20-1, (100 mg, 26%)

Sources & evidence

ORD record
ord-4c5fbf3a7ae04f21b91f31c15b3f3983
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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