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-((tetrahydrofuran-2-yl)methyl)urea

HRID 1801694Notes

Reaction equation

HRID 1801694 reaction equation
[O:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:6][NH:7][C:8]1[N:13]=[CH:12][C:11]([C:14]2[NH:22][C:21]3[C:20](=[O:23])[N:19]([CH2:24][CH2:25][CH3:26])[C:18](=[O:27])[N:17]([CH2:28][CH2:29][CH3:30])[C:16]=3[CH:15]=2)=[CH:10][CH:9]=1.[F:31][C:32]1[CH:37]=[CH:36][C:35]([N:38]=[C:39]=[O:40])=[CH:34][CH:33]=1>C1COCC1>[F:31][C:32]1[CH:37]=[CH:36][C:35]([NH:38][C:39](=[O:40])[N:7]([C:8]2[CH:9]=[CH:10][C:11]([C:14]3[NH:22][C:21]4[C:20](=[O:23])[N:19]([CH2:24][CH2:25][CH3:26])[C:18](=[O:27])[N:17]([CH2:28][CH2:29][CH3:30])[C:16]=4[CH:15]=3)=[CH:12][N:13]=2)[CH2:6][CH:2]2[CH2:3][CH2:4][CH2:5][O:1]2)=[CH:34][CH:33]=1

Participants

4

Reactant 2

HCID 709554-Fluorophenyl isocyanateHCID 598566296-(6-((Tetrahydrofuran-2-yl)methylamino)pyridin-3-yl)-1,3-dipropyl-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione

Product 1

HCID 248160963-(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-((tetrahydrofuran-2-yl)methyl)ureaYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
94 °C

Procedure

9b (30 mg) was suspended in THF (2 ml) in a pressure tube, 4-fluorophenyl isocyanate (300 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, washed with ether and purified by column (14 g silica gel, RT Scientific) (CH2Cl2:MeOH=100:0 to 98:2) to give the product (11b) (18 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), 1.53-2.00 (m, 8H), 3.60-4.20 (m, 9H), 6.85 (s, 1H), 7.15 (t, 2H, J=8.7 Hz), 7.51 (m, 3H), 8.30 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 8.94 (d, 1H, J=2.4 Hz), 10.69 (s, 1H), 12.50 (s, 1H). MS: m/z 549 (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
  6. custompurified by column (14 g silica gel, RT Scientific) (CH2Cl2:MeOH=100:0 to 98:2)

Sources & evidence

ORD record
ord-abd555a4f76d42e4b65177f4d142f8a6
Source dataset
uspto-grants-2013_01
Patent number
US08349848B2

Reaction notes

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