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

HRID 245620Notes

Reaction equation

HRID 245620 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:14]2[O:23][C:22](=[O:24])[C:21]3[C:16](=[C:17]([CH3:28])[CH:18]=[C:19]4[CH:27]=[N:26][NH:25][C:20]4=3)[N:15]=2)[N:5]([C:7]2[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][N:8]=2)[N:6]=1.[CH:29]([NH2:32])([CH3:31])[CH3:30]>C(#N)C.O>[CH:29]([NH:32][C:22]([C:21]1[C:16]([NH:15][C:14]([C:4]2[N:5]([C:7]3[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][N:8]=3)[N:6]=[C:2]([Br:1])[CH:3]=2)=[O:23])=[C:17]([CH3:28])[CH:18]=[C:19]2[C:20]=1[NH:25][N:26]=[CH:27]2)=[O:24])([CH3:31])[CH3:30]

Participants

4

Reactant 2

HCID 6363IsopropylamineHCID 579901597-[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-5-methyl-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one

Product 1

HCID 579901736-{[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-5-methyl-1H-indazole-7-carboxylic acid isopropylamide

Reagents, catalysts & solvents 1

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

Procedure

To a suspension of 600 mg of the above 7-[5-bromo-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-5-methyl-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one in 10 mL of acetonitrile/water (4:1, v/v) is added 1.11 mL (13.1 mmol) of isopropylamine. The reaction mixture is stirred for 9 hours at ambient temperature and then concentrated in vacuo. The residue is taken-up with brine and ethyl acetate. The phases are separated and the aqueous layer is washed with ethyl acetate. The combined organic layers are washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography (SiO2, hexane/ethyl acetate 1:2) affords 110 mg (16% over two steps) of the product as a white solid; LC/MS:518/520 (M+H)+, m.p.: 163-166° C.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe phases are separated
  3. washthe aqueous layer is washed with ethyl acetate
  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, hexane/ethyl acetate 1:2)

Sources & evidence

ORD record
ord-0b56a2576a05487ca0cc3b172f2c5e80
Source dataset
uspto-grants-2014_02
Patent number
US08658801B2

Reaction notes

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