Trifluoroacetic acid → Trifluoroacetic acid

HRID 1615875Notes

Reaction equation

HRID 1615875 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=O)(C)(C)C.Cl.C(N=C=NCCCN(C)C)C.[NH2:29][C:30]1[S:31][C:32]2[C:37]([N:38]=1)=[CH:36][CH:35]=[C:34]([C:39]1[CH:40]=[C:41]([CH:55]=[CH:56][CH:57]=1)[C:42]([NH:44][C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:53])[F:52])[CH:46]=1)=[O:43])[N:33]=2.[F:58][C:59]([F:64])([F:63])[C:60]([OH:62])=[O:61]>CN(C)C1C=CN=CC=1.CN(C=O)C.C(OCC)(=O)C.ClCCl>[F:53][C:51]([F:52])([F:54])[C:47]1[CH:46]=[C:45]([NH:44][C:42]([C:41]2[CH:40]=[C:39]([C:34]3[N:33]=[C:32]4[S:31][C:30]([NH:29][C:14]([CH:11]5[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]5)=[O:16])=[N:38][C:37]4=[CH:36][CH:35]=3)[CH:57]=[CH:56][CH:55]=2)=[O:43])[CH:50]=[CH:49][CH:48]=1.[C:60]([OH:62])([C:59]([F:64])([F:63])[F:58])=[O:61]

Participants

10

Reactant 4

HCID 6422Trifluoroacetic acidHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66552475HCID 66552475, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 49838987HCID 49838987, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (15 mg, 0.07 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (26 mg, 0.14 mmol), 4-dimethylaminopyridine (8 mg, 0.07 mmol) in DMF was added 3-(2-aminothiazolo[5,4-b]pyridin-5-yl)-N-(3-(trifluoromethyl)phenyl)benzamide (28 mg, 0.07 mmol). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with ethyl acetate (5 mL) and washed 1N aqueous HCl and brine. The organic layer was dried over MgSO4 and the solvent removed in vacuo. To a solution of the crude mixture in dichloromethane (1 mL) was added trifluoroacetic acid (30 μL, 0.34 mmol). The reaction mixture was stirred for 4 h. The majority of the organic solvent was removed in vacuo and the crude product was diluted with DMSO (1 mL) and purified by preparative HPLC to give title compound in a TFA salt form.

Workup

  1. washwashed 1N aqueous HCl and brine
  2. dry with materialThe organic layer was dried over MgSO4
  3. customthe solvent removed in vacuo
  4. stirringThe reaction mixture was stirred for 4 h
  5. customThe majority of the organic solvent was removed in vacuo
  6. additionthe crude product was diluted with DMSO (1 mL)
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-239e39693b5f44dbbb6bce7dbe66ca93
Source dataset
uspto-grants-2014_07
Patent number
US08765747B2

Reaction notes

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