2-Fluorophenyl isocyanate → 1-[4-(4-Amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-2-yl]-3-(2-fluoro-phenyl)-urea

HRID 736348Notes

Reaction equation

HRID 736348 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]=[C:9]=[O:10].[NH2:11][C:12]1[C:13]2[C:20]([C:21]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH2:29])[CH:24]=3)=[O:22])=[CH:19][N:18]([CH:30]([CH3:32])[CH3:31])[C:14]=2[N:15]=[CH:16][N:17]=1>N1C=CC=CC=1>[NH2:11][C:12]1[C:13]2[C:20]([C:21]([C:23]3[CH:28]=[CH:27][N:26]=[C:25]([NH:29][C:9]([NH:8][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])=[O:10])[CH:24]=3)=[O:22])=[CH:19][N:18]([CH:30]([CH3:32])[CH3:31])[C:14]=2[N:15]=[CH:16][N:17]=1

Participants

4

Reactant 2

HCID 855882-Fluorophenyl isocyanateHCID 68906075(4-Amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-(2-amino-pyridin-4-yl)-methanone

Product 1

HCID 689078141-[4-(4-Amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-pyridin-2-yl]-3-(2-fluoro-phenyl)-ureaYield 55.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
80 °C

Procedure

1-Fluoro-2-isocyanato-benzene (0.09 mL, 0.81 mmol) was added to a solution of (4-Amino-7-isopropyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-(2-amino-pyridin-4-yl)-methanone (0.20 g, 0.67 mmol) in pyridine (2 mL). The mixture was heated to 80° C. in a sealed tube for 2 h. The reaction mixture was quenched with water (10 mL) and extracted with hot EtOAc/MeOH (95:5, 3×10 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo. Purification by flash column chromatography (ethyl acetate/MeOH 99:1) afforded the title compound as a yellow solid (160 mg, 55%). MS: 434.2 (MH+); HPLC Rf: 5.83 min. (HPLC method 4); HPLC purity: 98%.

Workup

  1. customThe reaction mixture was quenched with water (10 mL)
  2. extractionextracted with hot EtOAc/MeOH (95:5, 3×10 mL)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by flash column chromatography (ethyl acetate/MeOH 99:1)

Sources & evidence

ORD record
ord-74bae46ce2b442739b49b629ee0392d2
Source dataset
uspto-grants-2009_09
Patent number
US07595325B2

Reaction notes

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