Sodium Hydroxide → HCID 178503033, compound

HRID 1525256Notes

Reaction equation

HRID 1525256 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 178476763HCID 178476763, compound2×

Product 1

HCID 178503033HCID 178503033, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 4-((R)-(4-fluorophenyl)(4-hydroxy-2-(1H-pyrazol-1-yl)pyrimidine-5-carboxamido)methyl)phenyl(methyl)phosphinate, 18-f, (7 g, 14 mmol) was dissolved in 50 ml of dioxane and treated with 5 ml of 3N NaOH. The mixture was heated at 80° C. for one hour. Then the mixture was concentrated under vacuum. The 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 (9.2 g of crude). The product can be further purified via prep-HPLC give 4 g of title product, 18-1, (Y=61%). 1H NMR (300 MHz, DMSO-d6): δ 10.32 (br, 1H), 8.62 (s, 1H), 8.43 (s, 1H), 8.05 (s, 1H), 7.46 (m, 2H), 7.37 (m, 4H), 7.20 (m, 2H), 6.72 (s, 1H), 6.33 (d, 1H), 1.50 (d, 3H). (M+H)+=468.1.

Workup

  1. concentrationThen the mixture was concentrated under vacuum
  2. additionThe residue was diluted with water
  3. washwashed with ethyl acetate
  4. customThe product can be further purified

Sources & evidence

ORD record
ord-494a1f159a484e5a931b5e15b5d86bf1
Source dataset
uspto-grants-2015_07
Patent number
US09079930B2

Reaction notes

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