p-Toluenesulfonic acid → (R)-6-(2-chloro-4-iodophenylamino)-N-(2,3-dihydroxypropoxy)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide

HRID 641603Notes

Reaction equation

HRID 641603 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:15]([CH3:16])[C:14](=[O:17])[N:13]([CH3:18])[C:12](=[O:19])[C:11]=1[C:20]([NH:22][O:23][CH2:24][C@H:25]1[CH2:29][O:28]C(C)(C)[O:26]1)=[O:21].C1COCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:15]([CH3:16])[C:14](=[O:17])[N:13]([CH3:18])[C:12](=[O:19])[C:11]=1[C:20]([NH:22][O:23][CH2:24][C@H:25]([OH:26])[CH2:29][OH:28])=[O:21]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 8028TetrahydrofuranHCID 25108894(R)-6-(2-chloro-4-iodophenylamino)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide

Product 1

HCID 25108895(R)-6-(2-chloro-4-iodophenylamino)-N-(2,3-dihydroxypropoxy)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(R)-6-(2-chloro-4-iodophenylamino)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide (Example 26, 140 mg, 0.24 mmol, 1 eq) was dissolved in 3 ml of MeOH and 3 ml of THF then p-toluenesulfonic acid (24 mg, 0.5 eq) was added. After stirring at RT for 6 hours the reaction was complete. Evaporation in vacuo, followed by HPLC purification gave the title compound as a white solid. (31 mg, 24%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.89 (s, 3 H) 3.21 (s, 3 H) 3.28-3.40 (m, 2 H) 3.65-3.74 (m, 2 H) 3.93 (dd, J=14.15, 6.82 Hz, 1 H) 4.61 (t, J=5.68 Hz, 1 H) 4.99 (d, J=4.04 Hz, 1 H) 7.14 (d, J=8.34 Hz, 1 H) 7.70 (dd, J=8.34, 1.77 Hz, 1 H) 7.98 (d, J=1.77 Hz, 1 H) 12.03 (s, 1 H) 12.50 (s, 1 H) [M+H] calc'd for C16H18ClIN4O6, 525; found, 525.

Workup

  1. customEvaporation in vacuo
  2. customfollowed by HPLC purification

Sources & evidence

ORD record
ord-ee3248d2d46c4034b4bb14a8d7b85bdc
Source dataset
uspto-grants-2010_04
Patent number
US07696218B2

Reaction notes

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