4-Fluorophenyl isocyanate → 3-(4-fluorophenyl)-1-(5-(2,3,4,5-tetrahydro-2,4-dioxo-1,3-dipropyl-1H-pyrrolo[3,2-d]pyrimidin-6-yl)pyridin-2-yl)-1-(2-methoxyethyl)urea

HRID 1801693Notes

Reaction equation

HRID 1801693 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][NH:5][C:6]1[N:11]=[CH:10][C:9]([C:12]2[NH:20][C:19]3[C:18](=[O:21])[N:17]([CH2:22][CH2:23][CH3:24])[C:16](=[O:25])[N:15]([CH2:26][CH2:27][CH3:28])[C:14]=3[CH:13]=2)=[CH:8][CH:7]=1.[F:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]=[C:37]=[O:38])=[CH:32][CH:31]=1>C1COCC1>[F:29][C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37](=[O:38])[N:5]([C:6]2[CH:7]=[CH:8][C:9]([C:12]3[NH:20][C:19]4[C:18](=[O:21])[N:17]([CH2:22][CH2:23][CH3:24])[C:16](=[O:25])[N:15]([CH2:26][CH2:27][CH3:28])[C:14]=4[CH:13]=3)=[CH:10][N:11]=2)[CH2:4][CH2:3][O:2][CH3:1])=[CH:32][CH:31]=1

Participants

4

Reactant 2

HCID 709554-Fluorophenyl isocyanateHCID 598566356-(6-(2-methoxyethylamino)pyridin-3-yl)-1,3-dipropyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione

Product 1

HCID 248160953-(4-fluorophenyl)-1-(5-(2,3,4,5-tetrahydro-2,4-dioxo-1,3-dipropyl-1H-pyrrolo[3,2-d]pyrimidin-6-yl)pyridin-2-yl)-1-(2-methoxyethyl)ureaYield 26.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
94 °C

Procedure

9a (25 mg) was suspended in THF (2 ml) in a pressure tube, 4-fluorophenyl isocyanate (200 mg) was added and the mixture was stirred at 94° C. for 3 days. After cooling to room temperature, the mixture was evaporated to almost dry and the solid was filtered and washed with ether (two peaks shown in HPLC, rt=8.0 min, rt=1.6 min). The solid was stirred with DCM, the solid (rt=8.0 min) was removed and the mother liquid was collected. After removal of the solvent, the residue was purified by column (14 g silica gel, RT Scientific) (CH2Cl2: MeOH=100:0 to 98:2) to give the product (11a) (9 mg). HPLC condition: MeOH 40%-95% gradient in 10 minutes then MeOH 95%. Retention Time=11.60 min. 1H NMR (DMSO, d6): 0.83-0.95 (m, 6H), 1.53-1.75 (m, 4H), 3.26 (s, 3H), 3.60 (t, 2H), 3.87 (t, 2H), 4.17 (t, 2H), 6.85 (s, 1H), 7.16 (t, 2H, J=8.7 Hz), 7.48 (m, 3H), 8.30 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 8.95 (d, 1H, J=2.4 Hz), 10.87 (s, 1H), 12.50 (s, 1H). MS: m/z 523 (M+H)+.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was evaporated
  3. customto almost dry
  4. filtrationthe solid was filtered
  5. washwashed with ether (two peaks shown in HPLC, rt=8.0 min, rt=1.6 min)
  6. stirringThe solid was stirred with DCM
  7. customthe solid (rt=8.0 min) was removed
  8. customthe mother liquid was collected
  9. customAfter removal of the solvent
  10. customthe residue was purified by column (14 g silica gel, RT Scientific) (CH2Cl2: MeOH=100:0 to 98:2)

Sources & evidence

ORD record
ord-9902ba7fbddf4a7d9334ced7bbd1e690
Source dataset
uspto-grants-2013_01
Patent number
US08349848B2

Reaction notes

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