4-Fluorophenyl isocyanate → 1-(2-(dimethylamino)ethyl)-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)urea

HRID 2377731Notes

Reaction equation

HRID 2377731 reaction equation
[CH3:1][N:2]([CH3:29])[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:30][C:31]1[CH:36]=[CH:35][C:34]([N:37]=[C:38]=[O:39])=[CH:33][CH:32]=1>C1COCC1>[CH3:29][N:2]([CH3:1])[CH2:3][CH2:4][N:5]([C:6]1[CH:7]=[CH:8][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:10][N:11]=1)[C:38]([NH:37][C:34]1[CH:35]=[CH:36][C:31]([F:30])=[CH:32][CH:33]=1)=[O:39]

Participants

4

Reactant 2

HCID 709554-Fluorophenyl isocyanateHCID 598566346-(6-(2-(dimethylamino)ethylamino)pyridin-3-yl)-1,3-dipropyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione

Product 1

HCID 248160941-(2-(dimethylamino)ethyl)-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)ureaYield 46.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

9c (35 mg) was suspended in THF (3 ml) in a pressure tube, 4-fluorophenyl isocyanate (130 mg) was added and the mixture was stirred at 85° C. for 3 days. After cooling to room temperature, the mixture was evaporated and the solid was stirred with ether and filtered The mother liquid contained most of the product. After removal of the solvent, the residue was purified by column (14 g silica gel, RT Scientific) (CH2Cl2: MeOH=100:0 to 95:5) to give the product (11c) (22 mg). HPLC condition: MeOH 40%-95% gradient in 10 minutes then MeOH 95%. Retention Time=7.20 min. 1H NMR (DMSO, d6): 0.83-0.93 (m, 6H), 1.53-1.71 (m, 4H), 2.28 (s, 6H), 2.50 (s, 4H), 3.87 (m, 4H), 4.14 (t, 1H, J=5.4 Hz), 6.83 (s, 1H), 7.15 (t, 2H, J=8.7 Hz), 7.52 (m, 3H), 8.24 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 8.92 (d, 1H, J=2.4 Hz), 11.54 (s, 1H). MS: m/z 536 (M+H)+.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe mixture was evaporated
  3. stirringthe solid was stirred with ether
  4. filtrationfiltered The mother liquid
  5. customAfter removal of the solvent
  6. customthe residue was purified by column (14 g silica gel, RT Scientific) (CH2Cl2: MeOH=100:0 to 95:5)

Sources & evidence

ORD record
ord-35b29bbd7f664778a9e60dca25234852
Source dataset
uspto-grants-2008_12
Patent number
US07470697B2

Reaction notes

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