Trifluoroacetic acid → Trifluoroacetic acid

HRID 1615874Notes

Reaction equation

HRID 1615874 reaction equation
[NH2:1][C:2]1[S:3][C:4]2[C:9]([N:10]=1)=[CH:8][CH:7]=[C:6]([C:11]1[CH:12]=[C:13]([CH:27]=[CH:28][CH:29]=1)[C:14]([NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=1)=[O:15])[N:5]=2.C([N:32]([CH2:35][CH3:36])[CH2:33][CH3:34])C.C(Cl)(=O)OC1C=CC([N+]([O-])=O)=CC=1.NC1CC[N:54]([C:57](OC(C)(C)C)=[O:58])[CH2:53]C1.[F:64][C:65]([F:70])([F:69])[C:66]([OH:68])=[O:67]>ClCCl>[NH:32]1[CH2:33][CH2:34][CH:53]([NH:54][C:57](=[O:58])[NH:1][C:2]2[S:3][C:4]3[C:9]([N:10]=2)=[CH:8][CH:7]=[C:6]([C:11]2[CH:12]=[C:13]([CH:27]=[CH:28][CH:29]=2)[C:14]([NH:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)=[O:15])[N:5]=3)[CH2:36][CH2:35]1.[C:66]([OH:68])([C:65]([F:70])([F:69])[F:64])=[O:67]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471Triethylamine2×HCID 821294-Nitrophenyl chloroformateHCID 12682914-Amino-1-Boc-piperidineHCID 66552475HCID 66552475, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 49838872HCID 49838872, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3-(2-aminothiazolo[5,4-b]pyridin-5-yl)-N-(3-(trifluoromethyl)phenyl)benzamide (50 mg, 0.12 mmol) and triethylamine (25 μL, 0.18 mmol) in dichloromethane (1.0 mL) was added 4-nitrophenyl carbonochloridate (26 mg, 0.13 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1 h. Tert-butyl 4-aminopiperidine-1-carboxylate (36 mg, 0.18 mmole) and triethylamine (25 μL, 0.18 mmol) were added to the reaction mixture. The reaction mixture was stirred for 4 h after which time the solvent was removed in vacuo. The reaction mixture was diluted with dichloromethane (5 mL) and washed with 1N aqueous HCl and brine. The organic layer was dried over MgSO4 and concentrated in vacuo. To a solution of the crude mixture in dichloromethane (1 mL) was added trifluoroacetic acid (40 μL, 0.60 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. stirringThe reaction mixture was stirred for 4 h after which time the solvent
  2. customwas removed in vacuo
  3. additionThe reaction mixture was diluted with dichloromethane (5 mL)
  4. washwashed with 1N aqueous HCl and brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. stirringThe reaction mixture was stirred for 4 h
  8. customThe majority of the organic solvent was removed in vacuo
  9. additionthe crude product was diluted with DMSO (1 mL)
  10. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-bc26a5e08aa44549b01a620e7b67d762
Source dataset
uspto-grants-2014_07
Patent number
US08765747B2

Reaction notes

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