p-Toluenesulfonic acid → 4-chloro-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one

HRID 1685193Notes

Reaction equation

[Cl:1][C:2]1[C:7]([CH2:8][C:9](OC)=[O:10])=[C:6]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=2[O:23][CH3:24])[N:5]=[CH:4][N:3]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:7]2[CH2:8][C:9](=[O:10])[N:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=3[O:23][CH3:24])[C:6]=2[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 10 °C

Procedure

Combine a solution of methyl 2-(4-chloro-6-(2,4-dimethoxybenzylamino)pyrimidin-5-yl)acetate (1.00 equiv; 2.23 mol; 783 g) in p-toluenesulfonic acid (0.5 equiv; 1.10 mol; 212 g) with Toluene (12 L) and stir at reflux. After 1 h, remove toluene in vacuo and extract with DCM. Wash the organic layer with saturated NaHCO3(aq) and brine, dry over Na2SO4, filter and concentrated in vacuo. Slurry the residue in methanol (2 L) and concentrate in vacuo to approximately 1 L. Cool the slurry to 10° C., filter, wash with cold methanol, and dry to obtain the title compound (1.65 mol; 527 g; 74.05%) as a yellow-orange solid. 1H NMR (400 MHz, CDCl3): 8.59 (s, 1H), 7.13 (d, J=8.4 Hz, 1H), 6.43 (d, J=2.0 Hz, 1H), 6.40 (d, J=8.5 Hz, 1H), 4.92 (d, s, 2H), 3.79 (s, 3H), 3.77 (s, 3H), 3.60 (s, 2H).

Workup

temperatureat reflux
customremove toluene in vacuo
extractionextract with DCM
washWash the organic layer with saturated NaHCO3(aq) and brine
dry with materialdry over Na2SO4
filtrationfilter
concentrationconcentrated in vacuo
concentrationconcentrate in vacuo to approximately 1 L
filtrationfilter
washwash with cold methanol
customdry

Sources & evidence

ORD record: ord-3f63e7b212284b27898a9a6b7465e2b7
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148387B2

Reaction notes

Loading…