Hydrochloric Acid → methyl 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)acetate dihydrochloride

HRID 1665997Notes

Reaction equation

HRID 1665997 reaction equation
[C:1]([C:3]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:4]=1[O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][C:16]([O:18][CH3:19])=[O:17])[N:10]=[CH:9]2)#[N:2].[ClH:25]>[Pd].CO>[ClH:25].[ClH:25].[NH2:2][CH2:1][C:3]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:4]=1[O:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH2:15][C:16]([O:18][CH3:19])=[O:17])[N:10]=[CH:9]2

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 57552286methyl 2-(5-(2-cyano-4-fluorophenoxy)-1H-indazol-1-yl)acetate

Product 1

HCID 66671265methyl 2-(5-(2-(aminomethyl)-4-fluorophenoxy)-1H-indazol-1-yl)acetate dihydrochlorideYield 93.8%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

Methyl 2-(5-(2-cyano-4-fluorophenoxy)-1H-indazol-1-yl)acetate (10.00 g, 30.74 mmol) was placed in a 2500 mL Parr hydrogenation vessel. Methanol (0.1M, 310 mL) and concentrated HCl (25.62 ml, 307.4 mmol) were added. 10% Pd/C (2.0 g, Degussa type) was added and the vessel was purged with hydrogen gas (three times, no vacuum evacuation was done). The vessel was charged with hydrogen gas at 40 psi and was left on the shaker for 18 hours. To the mixture was added additional 1.0 g of 10% Pd/C and the mixture was placed back in the Parr hydrogenator for an additional 18 hours. The mixture was filtered through a Celite pad and concentrated under reduced pressure (bath temperature kept below 20° C.). The residue was azeotroped with MeOH (3×100 mL). The bath temperature was raised to 40° C. after the third azeotrope. The residue (oil) was dried under high vacuum for 2 hours to provide the desired product as a yellow solid (11.6 g, 93.8%). MS (APCI+) m/z 330 (M+1) was detected. 1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 6.84-7.76 (m, 6H), 5.43 (s, 2H), 4.8 (br, 2H), 4.105 (q, 2H, J=5.6 Hz), 3.68 (s, 3H).

Workup

  1. customthe vessel was purged with hydrogen gas (three times
  2. additionThe vessel was charged with hydrogen gas at 40 psi
  3. additionTo the mixture was added additional 1.0 g of 10% Pd/C
  4. waitthe mixture was placed back in the Parr hydrogenator for an additional 18 hours
  5. filtrationThe mixture was filtered through a Celite pad
  6. concentrationconcentrated under reduced pressure (bath temperature kept below 20° C.)
  7. customThe residue was azeotroped with MeOH (3×100 mL)
  8. customThe residue (oil) was dried under high vacuum for 2 hours

Sources & evidence

ORD record
ord-4bfd2a3507474264a115542e1dc76ee3
Source dataset
uspto-grants-2011_10
Patent number
US08039639B2

Reaction notes

Loading…