1,1'-Carbonyldiimidazole → HCID 118093982, compound

HRID 1056952Notes

Reaction equation

HRID 1056952 reaction equation
[NH2:1][C:2]1[C:3]([O:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][C:30]=2[F:36])=[C:4]([C:9]2[C:10]3[CH:19]=[N:18][N:17](COCC[Si](C)(C)C)[C:11]=3[C:12](=[O:16])[N:13]([CH3:15])[CH:14]=2)[CH:5]=[CH:6][C:7]=1[NH2:8].C1N=CN([C:42](N2C=NC=C2)=[O:43])C=1>O1CCCC1.C(OCC)(=O)C.O>[F:36][C:30]1[CH:31]=[C:32]([F:35])[CH:33]=[CH:34][C:29]=1[O:28][C:3]1[C:2]2[NH:1][C:42](=[O:43])[NH:8][C:7]=2[CH:6]=[CH:5][C:4]=1[C:9]1[C:10]2[CH:19]=[N:18][NH:17][C:11]=2[C:12](=[O:16])[N:13]([CH3:15])[CH:14]=1

Participants

6

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 123716138HCID 123716138, compound

Product 1

HCID 118093982HCID 118093982, compoundYield 25.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 4-[3,4-diamino-2-(2,4-difluorophenoxyl)phenyl]-6-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1,6-dihydro-7H-pyrazolo[3,4-c]pyridin-7-one (80.0 mg, 0.156 mmol) in tetrahydrofuran (3.0 mL) was treated with N,N-carbonyldiimidazole (50.0 mg, 0.31 mmol) and stirred at 50° C. for 1 h. The reaction mixture was diluted with ethyl acetate and water. The organic layer was separated and washed with water and brine, dried with magnesium sulfate, filtered, and concentrated in vacuo to give the SEM-protected intermediate which was used without further purification. The crude intermediate was diluted with methylene chloride (4.0 mL) and trifluoroacetic acid (4.0 mL) and stirred at 40° C. for 2 h. The reaction mixture was concentrated, diluted with acetonitrile, adjusted to pH ˜7 with 1 M NaOH, and purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (16 mg, 20%). 1H NMR (500 MHz, DMSO-d6) δ 13.96 (br s, 1H), 11.03 (br s, 1H), 10.91 (br s, 1H), 7.68 (br s, 1H), 7.22-7.05 (m, 3H), 6.97 (d, J=8.0 Hz, 1H), 6.70 (dd, J=8.6, 8.6 Hz, 1H), 6.53-6.39 (m, 1H), 3.46 (s, 3H); LCMS calculated for C20H14F2N5O3 (M+H)+: m/z=410.1. found: 410.1.

Workup

  1. customThe organic layer was separated
  2. washwashed with water and brine
  3. dry with materialdried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give the SEM-protected intermediate which
  7. customwas used without further purification
  8. additionThe crude intermediate was diluted with methylene chloride (4.0 mL) and trifluoroacetic acid (4.0 mL)
  9. stirringstirred at 40° C. for 2 h
  10. concentrationThe reaction mixture was concentrated
  11. additiondiluted with acetonitrile
  12. custompurified via preparative LCMS (XBridge C18 column
  13. washeluting with a gradient of acetonitrile/water 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-036a85aba9ed4368b34b4a3bf95ca924
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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