Sodium Hydroxide → HCID 72700515, compound

HRID 591384Notes

Reaction equation

HRID 591384 reaction equation
[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=[N:10][C:11]([C:17]2[CH:18]=[C:19]([S:23]([NH:26][P:27](=[O:30])([OH:29])[OH:28])(=[O:25])=[O:24])[CH:20]=[N:21][CH:22]=2)=[N:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+:40]>C(O)C.O>[C:1]1([C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[C:9]([NH:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)=[N:10][C:11]([C:17]2[CH:18]=[C:19]([S:23]([NH:26][P:27](=[O:28])([O-:29])[O-:30])(=[O:24])=[O:25])[CH:20]=[N:21][CH:22]=2)=[N:12]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1.[Na+:40].[Na+:40]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 72543758HCID 72543758, compound

Product 1

HCID 72700515HCID 72700515, compoundYield 54.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a suspension of ((5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-yl)sulfonyl)phosphoramidic acid (2) (0.070 g, 0.13 mmol) in ethanol (5 mL) was added NaOH (9.95 mg, 0.249 mmol) in 1 mL of water. The reaction mixture was stirred under nitrogen atmosphere at room temperature for 2 h. The reaction mixture was concentrated to dryness and the residue washed with ethyl acetate (2×10 mL), acetone (2×10 mL) and acetonitrile (2×15 mL) to afford disodium (5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)quinazolin-2-yl)pyridin-3-yl)sulfonylphosphoramidate (4) (0.040 g, 0.068 mmol, 52% yield) as a yellow solid. 1H NMR (400 MHz, deuterium oxide) δ (ppm) 4.46 (s, 2H), 7.04 (d, J=7.78 Hz, 1H), 7.16 (d, J=6.27 Hz, 1H), 7.18-7.23 (m, 1H), 7.26 (d, J=6.27 Hz, 2H), 7.33 (d, J=6.78 Hz, 3H), 7.57-7.72 (m, 3H), 8.27 (d, J=4.27 Hz, 1H), 8.88 (br. s., 1H), 9.03 (s, 1H), 9.19 (s, 1H); 31P (162.0 MHz, DMSO-d6) δ (ppm) −5.19; LCMS Method I: retention time 1.61 min, [M+1]=549. HPLC Method K: Purity 94%, retention time 8.59 min. Elemental analysis: MF C25H19N6SPO5.2.3 Na.3.8 H2O, Calculated C, 45.03; H, 4.02; N, 12.60; Na, 7.79; H2O, 10.27; Found C, 44.90; H, 3.58; N, 12.40; Na, 7.79; H2O, 10.61.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. washthe residue washed with ethyl acetate (2×10 mL), acetone (2×10 mL) and acetonitrile (2×15 mL)

Sources & evidence

ORD record
ord-52bfbe548b884086b41f0103bf7d5011
Source dataset
uspto-grants-2016_01
Patent number
US09238666B2

Reaction notes

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