Hydrochloric Acid → 3-(2-(4-aminopiperidin-1-yl)pyrimidin-4-yl)-N,N-dimethyl-1H-indazole-5-carboxamide

HRID 1529446Notes

Reaction equation

HRID 1529446 reaction equation
[CH3:1][N:2]([CH3:40])[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[N:10](C1CCCCO1)[N:9]=[C:8]2[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([N:26]2[CH2:31][CH2:30][CH:29]([NH:32]C(=O)OC(C)(C)C)[CH2:28][CH2:27]2)[N:21]=1)=[O:4].Cl>CCOC(C)=O>[NH2:32][CH:29]1[CH2:30][CH2:31][N:26]([C:22]2[N:21]=[C:20]([C:8]3[C:7]4[C:11](=[CH:12][CH:13]=[C:5]([C:3]([N:2]([CH3:40])[CH3:1])=[O:4])[CH:6]=4)[NH:10][N:9]=3)[CH:25]=[CH:24][N:23]=2)[CH2:27][CH2:28]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86709796tert-butyl (1-(4-(5-(dimethylcarbamoyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-yl)carbamate

Product 1

HCID 679767933-(2-(4-aminopiperidin-1-yl)pyrimidin-4-yl)-N,N-dimethyl-1H-indazole-5-carboxamideYield 56.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl (1-(4-(5-(dimethylcarbamoyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrimidin-2-yl)piperidin-4-yl)carbamate (0.4 g, 0.728 mmol) in EtOAc (8 mL) was added HCl (4 N in dioxane, 8 mL) and the reaction was stirred at RT for 3 h The mixture was quenched with water and neutralized with NaHCO3 and extracted with EtOAc. The organic layer was separated and dried over Na2SO4, filtered and concentrated. The residue was purified with HPLC (5-50% MeCN in water with 0.1% TFA) to give 3-(2-(4-aminopiperidin-1-yl)pyrimidin-4-yl)-N,N-dimethyl-1H-indazole-5-carboxamide (150 mg, 52%) as an off white solid. MS (ESI, pos. ion) m/z: 366.2 (M+1); 1H NMR (300 MHz, DMSO-d6): −δ 13.88 (s, 1H), 8.53 (s, 1H), 8.48 (d, 2 H, J=5.1 Hz), 7.96 (s, 3H), 7.70 (d, 1 H, J=8.6 Hz), 7.52 (dd, 1 H, J=8.6, 1.4 Hz), 7.38 (d, 1 H, J=5.1 Hz), 4.77 (d, 2 H, J=13.6 Hz), 3.41 (bs, 1H), 3.09-3.20 (m, 2H), 3.03 (s, 6H), 2.03 (d, 2 H, J=10.5 Hz), 1.47-1.58 (m, 2H).

Workup

  1. customwas quenched with water and neutralized with NaHCO3
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified with HPLC (5-50% MeCN in water with 0.1% TFA)

Sources & evidence

ORD record
ord-52a59c7361604ea6851f837386fdeab4
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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