Diethyl cyanophosphonate → HCID 57496978, compound

HRID 272221Notes

Reaction equation

HRID 272221 reaction equation
O.O.Cl.[NH2:4][C:5]1[N:14]=[C:13]([NH2:15])[C:12]2[C:7](=[N:8][CH:9]=[C:10]([CH2:16][N:17]([CH3:27])[C:18]3[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=3)[N:11]=2)[N:6]=1.NC1N=C(N)C2C(=NC=C(CN(C3C=CC(C(O)=O)=CC=3)C)N=2)N=1.O.O.C(P(=O)(OCC)OCC)#N.CCN(C(C)C)C(C)C.C(O)(=O)C(O)=O.[CH2:79]([O:81][P:82]([CH2:87][CH2:88][NH2:89])(=[O:86])[O:83][CH2:84][CH3:85])[CH3:80]>CN(C=O)C>[CH2:84]([O:83][P:82]([CH2:87][CH2:88][NH:89][C:22](=[O:23])[C:21]1[CH:20]=[CH:19][C:18]([N:17]([CH2:16][C:10]2[N:11]=[C:12]3[C:7](=[N:8][CH:9]=2)[N:6]=[C:5]([NH2:4])[N:14]=[C:13]3[NH2:15])[CH3:27])=[CH:26][CH:25]=1)(=[O:86])[O:81][CH2:79][CH3:80])[CH3:85]

Participants

6

Reactant 4

HCID 76257Diethyl cyanophosphonateHCID 81531DiisopropylethylamineHCID 2733595Diethyl (2-aminoethyl)phosphonate oxalateHCID 1317271884-[(2,4-Diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoic acid hemihydrochloride dihydrate

Product 1

HCID 57496978HCID 57496978, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-[(2,4-diamino-pteridin-6-ylmethyl)-methyl-amino]-benzoic acid hemihydrochloride dihydrate (61.2 mg, 161 μmol) in DMF (2.8 mL) were added diethyl cyanophosphonate (31.8 μL, 210 μmol) and DIEA (27.8 μL, 161 μmol). The solution was stirred at ambient temperature for 4 hours, when diethyl(aminoethyl)phosphonate oxalate (43.8 mg, 161 μmol) was added. The solution was stirred for 3 additional hours, by which time complete consumption of the starting materials was observed. The reaction was worked up by removal of the solvent in vacuo and purifying the residue by silica gel chromatography using MeOH—CH2Cl2 (10-30%). The product collected from this chromatography step was sufficiently pure to be carried on to the next reaction. A small amount of the product (32 mg) was re-purified by RP HPLC on C18 column using H2O/acetonitrile (2-95%) to provide 19 mg (70%) of the pure product. 1H NMR (300 MHz, DMSO-d6) δ 1.21 (t, 6H, J=7 Hz), 1.95-2.05 (m, 2H), 3.20 (s, 3H), 3.13-3.22 (m, 2H), 3.98 (appt septet, 4H, J=7 Hz), 4.79 (s, 2H), 6.80 (d, 2H, J=9 Hz), 7.65 (d, 2H, J=9 Hz), 8.20 (br s, 1H), 8.60 (s, 1H). 31P (121.4 MHz, DMSO-d6) δ 28.9. MS (m/z) 489.2 [M+H]+, 511.2 [M+Na]+.

Workup

  1. stirringThe solution was stirred for 3 additional hours, by which time complete consumption of the starting materials
  2. customThe reaction was worked up by removal of the solvent in vacuo
  3. custompurifying the residue by silica gel chromatography
  4. customThe product collected from this chromatography step
  5. customto be carried on to the next reaction
  6. customA small amount of the product (32 mg) was re-purified by RP HPLC on C18 column

Sources & evidence

ORD record
ord-5204135f06d34e678b9c4120881a2964
Source dataset
uspto-grants-2008_11
Patent number
US07452901B2

Reaction notes

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