Hydrogen chloride-ethyl acetate → Ammonia

HRID 1045958Notes

Reaction equation

HRID 1045958 reaction equation
[Cl:1][C:2]1[C:3]([NH:22][C:23]2[CH:24]=[CH:25][CH:26]=[C:27]3[C:32]=2[C:31](=[O:33])[N:30]([CH3:34])[CH2:29][CH2:28]3)=[CH:4][C:5]([NH:8][C:9]2[C:10]([CH3:21])=[N:11][N:12](C(OC(C)(C)C)=O)[CH:13]=2)=[N:6][CH:7]=1.Cl.CCOC(C)=O>CCOC(C)=O>[NH3:6].[Cl:1][C:2]1[C:3]([NH:22][C:23]2[CH:24]=[CH:25][CH:26]=[C:27]3[C:32]=2[C:31](=[O:33])[N:30]([CH3:34])[CH2:29][CH2:28]3)=[CH:4][C:5]([NH:8][C:9]2[C:10]([CH3:21])=[N:11][NH:12][CH:13]=2)=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 67075912HCID 67075912, compound

Product 2

HCID 222AmmoniaHCID 178434558HCID 178434558, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

Using the general procedure of Example 12, tert-butyl 4-[[5-chloro-4-[(2-methyl-1-oxo-3,4-dihydroisoquinolin-8-yl)amino]pyridin-2-yl]amino]-3-methylpyrazole-1-carboxylate, 68 mg was obtained from tert-butyl 4-amino-3-methylpyrazole-1-carboxylate. To a stirred solution of tert-butyl 4-[[5-chloro-4-[(2-methyl-1-oxo-3,4-dihydroisoquinolin-8-yl)amino]pyridin-2-yl]amino]-3-methylpyrazole-1-carboxylate (68 mg) in EtOAc (0.6 ml) was added HCl/EtOAc (4M, 1.0 ml) and the mixture stirred at room temperature for 2.5 hours. The reaction mixture was diluted with EtOAc (5 ml) and quenched with aq. potassium bicarbonate (0.53 g, 3 ml). The aqueous phase was extracted with EtOAc (2×5 ml), the combined organic extracts dried (Na2SO4), filtered and concentrated under reduced pressure. Purification via a ‘catch and release’ method (2 g isolute flash SCX-2, eluting with 100% MeOH then methanolic ammonia 0.5M→7M) afforded the title compound which was combined with a second batch; 59 mg. 1H NMR spectrum (methanol-d3) 2.03 (s, 3H), 2.84 (t, 2H), 3.00 (s, 3H), 3.46 (t, 2H), 6.47 (s, 1H), 6.72 (dd, 1H), 7.19 (dd, 1H), 7.23 (dd, 1H), 7.44 (bs, 1H), 7.71 (s, 1H); Mass spectrum: ESI+ MH+ 383.

Workup

  1. customquenched with aq. potassium bicarbonate (0.53 g, 3 ml)
  2. extractionThe aqueous phase was extracted with EtOAc (2×5 ml)
  3. dry with materialthe combined organic extracts dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification via a ‘catch and release’ method (2 g isolute flash SCX-2
  7. washeluting with 100% MeOH

Sources & evidence

ORD record
ord-9c867d89e460479697970a01e0adbe05
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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