Sodium Hydroxide → 2-[(2-{4-[(2,4-Diaminopteridin-6-ylmethyl)methylamino]benzoylamino}ethyl)-phenoxyphosphinoyloxy]propionic acid

HRID 2378850Notes

Reaction equation

HRID 2378850 reaction equation
C([O:3][C:4](=[O:43])[CH:5]([O:7][P:8]([CH2:17][CH2:18][NH:19][C:20](=[O:42])[C:21]1[CH:26]=[CH:25][C:24]([N:27]([CH2:29][C:30]2[N:31]=[C:32]3[C:37](=[N:38][CH:39]=2)[N:36]=[C:35]([NH2:40])[N:34]=[C:33]3[NH2:41])[CH3:28])=[CH:23][CH:22]=1)([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:9])[CH3:6])C.[OH-].[Na+]>CN(C=O)C.C(#N)C.O>[NH2:40][C:35]1[N:34]=[C:33]([NH2:41])[C:32]2[C:37](=[N:38][CH:39]=[C:30]([CH2:29][N:27]([CH3:28])[C:24]3[CH:25]=[CH:26][C:21]([C:20]([NH:19][CH2:18][CH2:17][P:8]([O:10][C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=4)([O:7][CH:5]([CH3:6])[C:4]([OH:43])=[O:3])=[O:9])=[O:42])=[CH:22][CH:23]=3)[N:31]=2)[N:36]=1

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 729847782-[(2-{4-[(2,4-Diaminopteridin-6-ylmethyl)methylamino]benzoylamino}ethyl)phenoxy-phosphinoyloxy]propionic acid ethyl ester

Product 1

HCID 866031932-[(2-{4-[(2,4-Diaminopteridin-6-ylmethyl)methylamino]benzoylamino}ethyl)-phenoxyphosphinoyloxy]propionic acidYield 71.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-[(2 {4-[(2,4-diaminopteridin-6-ylmethyl)methyl-amino]benzoylamino}ethyl)phenoxy-phosphinoyloxy]propionic acid ethyl ester (mixture of diastereomers at phosphorus; 40.0 mg, 65.7 μmol) in DMF (0.4 mL), acetonitrile (0.2 mL) and water (0.2 mL) was added aqueous sodium hydroxide (1 N. 131.4 μL). The solution was stirred at ambient temperature for 4 hours. The solvents were removed in vacuo and the crude product was purified by RP HPLC on C18 column using H2O/acetonitrile (2-95%) to provide 23.7 mg (71.3%) of the pure product. 1H NMR (300 MHz, DMSO-d6) δ 1.30 (d, 2H, J=6.9 Hz), 1.79 (m, 2H), 3.21 (s, 3H), 3.37 (m, 2H), 4.61 (m, 1H), 4.81 (s, 2H), 6.79 (d, 2H, J=8.7 Hz), 7.64 (d, 2H, J=9.7 Hz), 8.25 (br 5, 1H), 8.63 (s3 1H); 31P (121.4 MHz, DMSO-d6) δ 25.1. MS (m/z) 505.2 [M+H]+.

Workup

  1. customThe solvents were removed in vacuo
  2. customthe crude product was purified by RP HPLC on C18 column

Sources & evidence

ORD record
ord-8cbcf9567c6d4a0f84a9f2bc6b4c886b
Source dataset
uspto-grants-2008_12
Patent number
US07470724B2

Reaction notes

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