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

HRID 245632Notes

Reaction equation

HRID 245632 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[CH:29]=[N:28][NH:27][C:5]2=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[N:13]([C:19]3[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][N:20]=3)[N:14]=[C:15]([O:17][CH3:18])[CH:16]=1)[O:8][C:7]2=[O:26].[CH3:30][C:31]1([NH2:35])[CH2:34][S:33][CH2:32]1>CN(C)C=O>[CH3:30][C:31]1([NH:35][C:7]([C:6]2[C:11]([NH:10][C:9]([C:12]3[N:13]([C:19]4[C:24]([Cl:25])=[CH:23][CH:22]=[CH:21][N:20]=4)[N:14]=[C:15]([O:17][CH3:18])[CH:16]=3)=[O:8])=[C:2]([Cl:1])[CH:3]=[C:4]3[C:5]=2[NH:27][N:28]=[CH:29]3)=[O:26])[CH2:34][S:33][CH2:32]1

Participants

4

Reactant 2

HCID 552816773-Methylthietan-3-amineHCID 579901685-chloro-7-[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazol-3-yl]-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one

Product 1

HCID 579901485-chloro-6-{[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazole-3-carbonyl]-amino}-1H-indazole-7-carboxylic acid (3-methyl-thietan-3-yl)-amideYield 44.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 500 mg (1.16 mmol) of the above 5-chloro-7-[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazol-3-yl]-1H-8-oxa-1,2,6-triaza-cyclopenta[a]naphthalen-9-one in 10 mL of N,N-dimethylformamide is added 396 mg (3.49 mmol) of 3-methyl-thietan-3-ylamine. The reaction is stirred at 60° C. for 72 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 three times 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, hexanes/ethyl acetate 1:2) affords 276 mg (44%) of the product as a white solid; LC/MS:532/534 (M+H)+, m.p.: 162-165° C.

Workup

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

Sources & evidence

ORD record
ord-d9b9f75409554070854850951f3f9eaf
Source dataset
uspto-grants-2014_02
Patent number
US08658801B2

Reaction notes

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