Hydrochloric Acid → (R)-6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)-N-(piperidin-3-yl)pyrazin-2-amine

HRID 1529314Notes

Reaction equation

HRID 1529314 reaction equation
[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[C:20]2[N:25]=[C:24]([NH:26][C@@H:27]3[CH2:32][CH2:31][CH2:30][N:29](C(OC(C)(C)C)=O)[CH2:28]3)[CH:23]=[N:22][CH:21]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2].Cl>CCOC(C)=O>[CH:1]([O:4][C:5]1[N:10]=[C:9]([C:11]2[CH:12]=[C:13]3[C:17](=[CH:18][CH:19]=2)[NH:16][CH:15]=[C:14]3[C:20]2[N:25]=[C:24]([NH:26][C@@H:27]3[CH2:32][CH2:31][CH2:30][NH:29][CH2:28]3)[CH:23]=[N:22][CH:21]=2)[CH:8]=[N:7][CH:6]=1)([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67960038(R)-tert-butyl 3-(6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate

Product 1

HCID 67959856(R)-6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)-N-(piperidin-3-yl)pyrazin-2-amine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of (R)-tert-butyl 3-(6-(5-(6-isopropoxy-pyrazin-2-yl)-1-tosyl-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate (0.250 g, 0.365 mmol) in 1-4-dioxane (3.6 mL), 1N NaOH (3.6 mL) was added and heated at 100° C. for 2 h. The reaction mixture was quenched with ice cold water and precipitate was formed. The precipitate was collected by filtration, washed with ice cold water and dried to give pure (R)-tert-butyl 3-(6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate (180 mg, 93%). MS (ESI, pos. ion) m/z: 530.0 (M+1). To a solution of (R)-tert-butyl 3-(6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)pyrazin-2-ylamino)piperidine-1-carboxylate (180 mg, 1.25 mmol) in EtOAc (5.0 mL) was treated with HCl in EtOAc (5.0 mL) and stirred at RT for 3 h. The reaction mixture was quenched with water, neutralized with NaHCO3, extracted with EtOAc. The organic layer was separated, dried over Na2SO4 and evaporated to dryness. The crude solid was re-crystallized in acetone to obtain (R)-6-(5-(6-isopropoxypyrazin-2-yl)-1H-indol-3-yl)-N-(piperidin-3-yl)pyrazin-2-amine. MS (ESI, pos. ion) m/z: 430.0 (M+1).

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. customevaporated to dryness
  6. customThe crude solid was re-crystallized in acetone

Sources & evidence

ORD record
ord-e7a978a98ea74db19f228d3c5f75c608
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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