Triethylamine → 6-{[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carbonyl]-amino}-5-cyano-1H-indazole-7-carboxylic acid bicyclopropyl-1-ylamide

HRID 245613Notes

Reaction equation

HRID 245613 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]([C:27]#[N:28])[CH:17]=[C:18]5[CH:26]=[N:25][NH:24][C:19]5=4)[N:14]=3)=[CH:11][C:10]([C:29]([F:32])([F:31])[F:30])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.Cl.[C:34]1([NH2:40])([CH:37]2[CH2:39][CH2:38]2)[CH2:36][CH2:35]1.C(N(CC)CC)C>CN(C)C=O>[C:34]1([NH:40][C:21]([C:20]2[C:15]([NH:14][C:13]([C:12]3[N:8]([C:3]4[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=4)[N:9]=[C:10]([C:29]([F:31])([F:30])[F:32])[CH:11]=3)=[O:22])=[C:16]([C:27]#[N:28])[CH:17]=[C:18]3[C:19]=2[NH:24][N:25]=[CH:26]3)=[O:23])([CH:37]2[CH2:39][CH2:38]2)[CH2:36][CH2:35]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 53433499(1,1'-Bi(cyclopropan))-1-amine hydrochlorideHCID 579901177-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-9-oxo-1,9-dihydro-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalene-5-carbonitrile

Product 1

HCID 579901396-{[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazole-3-carbonyl]-amino}-5-cyano-1H-indazole-7-carboxylic acid bicyclopropyl-1-ylamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 500 mg of the above 7-[2-(3-chloro-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-9-oxo-1,9-dihydro-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalene-5-carbonitrile in 8 mL of N,N-dimethylformamide is added 218 mg (1.63 mmol) of bicyclopropyl-1-ylamine hydrochloride and 303 μL (2.18 mmol) of triethylamine. The reaction is stirred at 60° C. for 24 hours and then concentrated in vacuo. The residue is taken-up with water and ethyl acetate. The phases are separated and the aqueous layer is washed with ethyl acetate. The combined organic layers are washed several times with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by flash chromatography (SiO2, hexanes/ethyl acetate 3:9) affords 76 mg (12% over two steps) of the product as white solid; LC/MS: 555/557 (M+H)+.

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 several times with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash chromatography (SiO2, hexanes/ethyl acetate 3:9)

Sources & evidence

ORD record
ord-b4e370db32ee404585341ad93aa80851
Source dataset
uspto-grants-2014_02
Patent number
US08658801B2

Reaction notes

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