Isopropylamine → 6-{[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazole-3-carbonyl]-amino}-5-methyl-1H-indazole-7-carboxylic acid isopropylamide

HRID 245615Notes

Reaction equation

HRID 245615 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:13]3[O:22][C:21](=[O:23])[C:20]4[C:15](=[C:16]([CH3:27])[CH:17]=[C:18]5[CH:26]=[N:25][NH:24][C:19]5=4)[N:14]=3)=[CH:11][C:10]([O:28][CH3:29])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.[CH:30]([NH2:33])([CH3:32])[CH3:31]>C(#N)C.O>[CH:30]([NH:33][C:21]([C:20]1[C:15]([NH:14][C:13]([C:12]2[N:8]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=3)[N:9]=[C:10]([O:28][CH3:29])[CH:11]=2)=[O:22])=[C:16]([CH3:27])[CH:17]=[C:18]2[C:19]=1[NH:24][N:25]=[CH:26]2)=[O:23])([CH3:32])[CH3:31]

Participants

4

Reactant 2

HCID 6363IsopropylamineHCID 579901547-[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazol-3-yl]-5-methyl-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one

Product 1

HCID 249949016-{[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazole-3-carbonyl]-amino}-5-methyl-1H-indazole-7-carboxylic acid isopropylamide

Reagents, catalysts & solvents 1

HCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 500 mg of the above 7-[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazol-3-yl]-5-methyl-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one in 10 mL of 4:1 (v/v) mixture of acetonitrile/water is added 1.0 mL (12.2 mmol) of isopropylamine. The reaction mixture is stirred during 1 hour at ambient temperature and for 2.5 hours at 60° C. and then concentrated in vacuo. The residue is taken-up with brine and tert-butylmethylether. The phases are separated and the aqueous layer is washed with tert-butylmethylether. The combined organic layers are washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography (SiO2, hexanes/ethyl acetate 3:7) affords 118 mg (19% over two steps) of the product as white solid; LC/MS:468/470 (M+H)+, m.p.: 148-151° C.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe phases are separated
  3. washthe aqueous layer is washed with tert-butylmethylether
  4. washThe combined organic layers are washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash chromatography (SiO2, hexanes/ethyl acetate 3:7)

Sources & evidence

ORD record
ord-176c057af1db4515b95ad09abfdbf258
Source dataset
uspto-grants-2014_02
Patent number
US08658801B2

Reaction notes

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