Hydrochloric Acid → Gdc-0623

HRID 2076199Notes

Reaction equation

HRID 2076199 reaction equation
C([O:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[CH:12][C:13]2[N:14]([CH:25]=[N:26][CH:27]=2)[C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=1[F:24])=[O:9])=C.Cl>CO>[OH:3][CH2:4][CH2:5][O:6][NH:7][C:8]([C:10]1[CH:11]=[CH:12][C:13]2[N:14]([CH:25]=[N:26][CH:27]=2)[C:15]=1[NH:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][C:18]=1[F:24])=[O:9]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 591401665-(2-Fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxyethoxy)-amide

Product 1

HCID 42642654Gdc-0623Yield 91.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
45 °C

Procedure

To a suspension of 5-(2-fluoro-4-iodophenylamino)-imidazo[1,5-a]pyridine-6-carboxylic acid (2-vinyloxyethoxy)-amide (58.36 g, 0.12 mol) in methanol (600 mL) was added aqueous hydrochloric acid (242 mL, 1M, 0.242 mol). The reaction mixture was stirred and warmed to 45° C. for 1 hr during which time the solids dissolved. The reaction mixture was then cooled to room temperature, and concentrated in vacuo to remove the methanol. The resultant residue was treated with aqueous saturated sodium hydrogen carbonate and stirred at room temperature for 1 hr before collecting crude product by filtration, and drying at 55° C. over phosphorus (V) oxide under vacuum for 24 hr. The crude product was crystallized from IPA:H2O (1:1, v/v) (800 mL) with slow cooling and mechanical stirring. The product was collected by filtration and washed cold IPA:H2O (1:1, v/v) (100 mL) before being dried in vacuo at 55° C. to yield the title compound as a light brown solid (50.2 g, 90%). LCMS (Method A): RT=5.58 min, [M+H]+=457. 1H NMR (DMSO-d6, 400 MHz) 8.05 (1H, s), 7.58 (1H, dd, J=10.69, 1.92 Hz), 7.43 (1H, s), 7.39 (1H, d, J=9.33 Hz), 7.31-7.28 (1H, m), 6.89 (1H, d, J=9.31 Hz), 6.34 (1H, t, J=8.68 Hz), 4.64 (1H, s), 3.64 (2H, t, J=4.78 Hz), 3.46 (2H, m).

Workup

  1. dissolutiondissolved
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. customto remove the methanol
  5. additionThe resultant residue was treated with aqueous saturated sodium hydrogen carbonate
  6. stirringstirred at room temperature for 1 hr
  7. custombefore collecting crude product
  8. filtrationby filtration
  9. dry with materialdrying at 55° C. over phosphorus (V) oxide under vacuum for 24 hr
  10. customThe crude product was crystallized from IPA:H2O (1:1
  11. temperaturev/v) (800 mL) with slow cooling
  12. filtrationThe product was collected by filtration
  13. washwashed cold IPA:H2O (1:1
  14. customv/v) (100 mL) before being dried in vacuo at 55° C.

Sources & evidence

ORD record
ord-39b8c4ad0dca46dca8e3ac30abe2d090
Source dataset
uspto-grants-2011_04
Patent number
US07923456B2

Reaction notes

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