Sodium Hydroxide → HCID 178503032, compound

HRID 1525261Notes

Reaction equation

HRID 1525261 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:21][C:22]([C:24]2[C:25]([OH:35])=[N:26][C:27]([N:30]3[CH:34]=[CH:33][CH:32]=[N:31]3)=[N:28][CH:29]=2)=[O:23])[C:9]2[CH:14]=[CH:13][C:12]([P:15]([CH3:20])(=[O:19])[O:16]CC)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.[OH-].[Na+]>O1CCOCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([NH:21][C:22]([C:24]2[C:25]([OH:35])=[N:26][C:27]([N:30]3[CH:34]=[CH:33][CH:32]=[N:31]3)=[N:28][CH:29]=2)=[O:23])[C:9]2[CH:10]=[CH:11][C:12]([P:15]([CH3:20])(=[O:16])[OH:19])=[CH:13][CH:14]=2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 178476762HCID 178476762, compound2×

Product 1

HCID 178503032HCID 178503032, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 4-((S)-(4-fluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinate, 19-e, (12 g, 0.024 mol) was dissolved in 100 ml of dioxane and treated with 4 ml of 3N NaOH. The mixture was heated at 80° C. for one hour. The mixture was then concentrated under vacuum. The resulting residue was diluted with water and washed with ethyl acetate. The aqueous layer was acidified with conc. HCl to pH=1 and the expected product crashed out, 19-1, (9.2 g of crude). The product can be further purified via prep-HPLC (3.5 g). 1H NMR (300 MHz, DMSO-d6): δ 8.62 (s, 1H), 8.43 (s, 1H), 8.07 (s, 1H), 7.46 (m, 2H), 7.38 (m, 4H), 7.21 (m, 2H), 6.73 (s, 1H), 6.38 (d, 1H), 1.52 (d, 3H). (M+H)+=468.1.

Workup

  1. concentrationThe mixture was then concentrated under vacuum
  2. additionThe resulting residue was diluted with water
  3. washwashed with ethyl acetate
  4. customThe product can be further purified via prep-HPLC (3.5 g)

Sources & evidence

ORD record
ord-c4027694ca184786b24a73e2be1a86a4
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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