Hydrochloric Acid → N-tert-butyl-2-(5-isopropyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

HRID 246770Notes

Reaction equation

HRID 246770 reaction equation
C(OC[N:9]1[C:13]2=[N:14][CH:15]=[C:16]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[C:24]([CH:27]([CH3:29])[CH3:28])[CH:25]=4)[N:20]([CH3:30])[N:19]=3)[N:17]=[C:12]2[C:11]([C:31](=[O:37])[NH:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[CH:10]1)(=O)C(C)(C)C.[OH-].[K+].Cl>O1CCOCC1.O>[C:33]([NH:32][C:31]([C:11]1[C:12]2[C:13](=[N:14][CH:15]=[C:16]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[C:24]([CH:27]([CH3:28])[CH3:29])[CH:25]=4)[N:20]([CH3:30])[N:19]=3)[N:17]=2)[NH:9][CH:10]=1)=[O:37])([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 71279754(7-(tert-butylcarbamoyl)-2-(5-isopropyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-5-yl)methyl pivalate

Product 1

HCID 71279817N-tert-butyl-2-(5-isopropyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamideYield 32.3%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To a stirred solution of (7-(tert-butylcarbamoyl)-2-(5-isopropyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazin-5-yl)methyl pivalate (0.2 g, crude) in dioxane/water (5 mL/10 mL) was added KOH (0.23 g, 4.1 mmol). The mixture was stirred at room temperature for 3 hours. Then the reaction mixture treated with 1N HCl to pH=3-4. The solvent was removed under reduced pressure and the residue triturated with water (15 mL) and dried to give a crude product which was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 62% acetonitrile/38% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 64% acetonitrile/36% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.) to give N-tert-butyl-2-(5-isopropyl-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (0.05 g) as a yellow solid. LCMS: (M+H)+=391; 1H NMR (300 MHz, CD3OD): δ 9.05 (s, 1H), 8.29 (s, 1H), 8.16 (s, 1H), 7.61 (d, 1H, J=8.7 Hz), 7.48 (dd, 1H, J1=8.7 Hz, J2=1.5 Hz), 4.18 (s, 3H), 3.19-3.02 (m, 1H), 1.58 (s, 9H), 1.35 (d, 6H, J=6.6 Hz).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue triturated with water (15 mL)
  3. customdried
  4. customto give a crude product which
  5. customwas purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm
  6. wait62% acetonitrile/38% water (0.1% trifluoroacetic acid, v/v) initially, and then proceed to 64% acetonitrile/36% water (0.1% trifluoroacetic acid, v/v) in a linear fashion after just 9 min.

Sources & evidence

ORD record
ord-d898ba9593bb407189d7b36417156902
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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