Hydrochloric Acid → HCID 66770470, compound

HRID 1256260Notes

Reaction equation

HRID 1256260 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([F:19])[CH:15]=[CH:14][C:13]=2[C:12]2=[N:20][N:21]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:22]([NH:23][CH:24]3[CH2:29][CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25]3)=[C:11]2[N:10]=1.CO.Cl.C(=O)(O)[O-].[Na+]>O1CCOCC1.C1COCC1>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[C:18]2[CH:17]=[C:16]([F:19])[CH:15]=[CH:14][C:13]=2[C:12]2=[N:20][N:21]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[C:22]([NH:23][CH:24]3[CH2:25][CH2:26][NH:27][CH2:28][CH2:29]3)=[C:11]2[N:10]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 516892Sodium BicarbonateHCID 67494626HCID 67494626, compound

Product 1

HCID 66770470HCID 66770470, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

340 mg of 2-methylpropan-2-yl 4-{[5-(2,6-difluorophenyl)-7-fluoro-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinolin-3-yl]amino}piperidine-1-carboxylate are introduced into 16 ml of methanol and 1.5 ml of THF. After cooling to 0° C. using an ice bath, 2.7 ml of a 4N solution of hydrochloric acid in dioxane are added and the mixture is stirred at RT for 5 h. It is poured into 200 ml of saturated sodium bicarbonate solution and then extracted with ethyl acetate, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a DCM/methanol/aqueous ammonia mixture (90/10/1 by vol.), to give 180 mg of 5-(2,6-difluorophenyl)-7-fluoro-N-(piperidin-4-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinolin-3-amine (yellow solid), LC-MS-DAD-ELSD: 528=(M+H).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under RP
  5. customThe product is purified by flash chromatography on silica gel (15-40 μm)
  6. washeluting with a DCM/methanol/aqueous ammonia mixture (90/10/1 by vol.)

Sources & evidence

ORD record
ord-16b5dc81eab54250aff43620e8706862
Source dataset
uspto-grants-2013_06
Patent number
US08461175B2

Reaction notes

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