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

HRID 245630Notes

Reaction equation

HRID 245630 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:28]=[N:27][NH:26][C:5]2=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[N:13]([C:18]3[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][N:19]=3)[N:14]=[C:15]([Cl:17])[CH:16]=1)[O:8][C:7]2=[O:25].Cl.[C:30]1([NH2:36])([CH:33]2[CH2:35][CH2:34]2)[CH2:32][CH2:31]1.C(N(CC)CC)C>CN(C)C=O>[C:30]1([NH:36][C:7]([C:6]2[C:11]([NH:10][C:9]([C:12]3[N:13]([C:18]4[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][N:19]=4)[N:14]=[C:15]([Cl:17])[CH:16]=3)=[O:8])=[C:2]([Cl:1])[CH:3]=[C:4]3[C:5]=2[NH:26][N:27]=[CH:28]3)=[O:25])([CH:33]2[CH2:35][CH2:34]2)[CH2:32][CH2:31]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 53433499(1,1'-Bi(cyclopropan))-1-amine hydrochlorideHCID 57990091HCID 57990091, compound

Product 1

HCID 579901865-chloro-6-{[5-chloro-2-(3-chloro-pyridin-2-yl)-2H-pyrazole-3-carbonyl]-amino}-1H-indazole-7-carboxylic acid bicyclopropyl-1-ylamideYield 91.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 400 mg (0.78 mmol) of the above 5-chloro-7-[5-chloro-2-(3-chloro-pyridin-2-yl)-2H-pyrazol-3-yl]-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one in 8 mL of N,N-dimethylformamide is added 262 mg (1.96 mmol) of bicyclopropyl-1-ylamine hydrochloride and 273 μL (1.96 mmol) of triethylamine. The reaction is stirred at 50° C. for 16 hours and then concentrated in vacuo. The residue is taken-up with water and tert-butylmethylether. The phases are separated and the aqueous layer is washed twice 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 1:1 to 1:2, gradient) affords 380 mg (91%) of the product as a white solid; LC/MS:530/532 (M+H)+, m.p.: 173-175° C.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe phases are separated
  3. washthe aqueous layer is washed twice 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 1:1 to 1:2, gradient)

Sources & evidence

ORD record
ord-da2766bec057413a91b63f9aa4298bb8
Source dataset
uspto-grants-2014_02
Patent number
US08658801B2

Reaction notes

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