Trimethyl phosphite → [5-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl]phosphonic acid dimethyl ester

HRID 1922771Notes

Reaction equation

HRID 1922771 reaction equation
Br[CH2:2][C:3]1[S:4][C:5]2[N:6]=[C:7]([N:18]3[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=4[N:20]=[C:19]3[CH2:27][CH3:28])[N:8]=[C:9]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[C:10]=2[N:11]=1.[CH3:29][O:30][P:31]([O:34]C)[O:32][CH3:33]>>[CH3:29][O:30][P:31]([CH2:2][C:3]1[S:4][C:5]2[N:6]=[C:7]([N:18]3[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=4[N:20]=[C:19]3[CH2:27][CH3:28])[N:8]=[C:9]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)[C:10]=2[N:11]=1)(=[O:34])[O:32][CH3:33]

Participants

3

Reactant 2

HCID 8472Trimethyl phosphiteHCID 596061112-Bromomethyl-5-(2-ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine

Product 1

HCID 59606043[5-(2-Ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidin-2-ylmethyl]phosphonic acid dimethyl esterYield 87%

Conditions

Temperature
120 °C

Procedure

A mixture of 2-bromomethyl-5-(2-ethylbenzoimidazol-1-yl)-7-morpholin-4-ylthiazolo[5,4-d]pyrimidine (670 mg, 1.46 mmol) in trimethylphosphite (10 mL) was heated to reflux (120° C.) for 1 h then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-2%) then (Si—PCC, MeOH:EtOAc, 0-5%) affording the title compound as a yellow solid (620 mg, 87%)._LCMS (method H): RT 2.46 min, [M+H]+ 489.3

Workup

  1. temperaturewas heated
  2. concentrationthen concentrated in vacuo
  3. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:DCM, 0-2%)

Sources & evidence

ORD record
ord-6eed172d0dca4c4fb713fc570fac5008
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

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