Trifluoroacetic acid → HCID 10167564, compound

HRID 1371000Notes

Reaction equation

HRID 1371000 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[S:16][C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.[O:31]1C[CH:32]1[CH2:34][N:35]1[C:43]2[CH2:42][CH2:41][N:40]([C:44](=[O:46])[CH3:45])[CH2:39][C:38]=2[C:37]([C:47]2[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=2)=[N:36]1>ClCCl>[S:16]1[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[N:19]=[C:15]1[NH:14][CH:11]1[CH2:10][CH2:9][N:8]([CH2:6][CH:32]([OH:31])[CH2:34][N:35]2[C:43]3[CH2:42][CH2:41][N:40]([C:44](=[O:46])[CH3:45])[CH2:39][C:38]=3[C:37]([C:47]3[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=3)=[N:36]2)[CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 222938171-[1-Oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanoneHCID 71629874HCID 71629874, compound

Product 1

HCID 10167564HCID 10167564, compoundYield 66.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 220 mg (0.66 mmol) of 4-(benzothiazol-2-ylamino)-piperidine-1-carboxylic acid tert-butyl ester in dichloromethane (2 mL) was treated with trifluoroacetic acid (0.5 mL) at room temperature overnight. The solvent was then removed and the crude product dissolved in MeOH and stirred over 100 mg of sodium bicarbonate for 1 h. The solid was filtered off and the filtrate concentrated. The crude piperidine was then dissolved in 4 mL EtOH and treated with 220 mg (0.60 mmol) of 1-[1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone. The solution was heated to 60° C. overnight. The solvent was then removed by rotary evaporation and the crude product was purified by column chromatography (silica, 0-10% MeOH/EtOAc) to afford 240 mg (66%) of a white solid. MS (electrospray): exact mass calculated for C30H33F3N6O2S: 598.23; m/z found, 599.3 [M+H]+. 1H NMR (CDCl3, 400 MHz, a mixture of amide rotamers): 7.78 (d, J=8.22 Hz, 1H), 7.72 and 7.68 (A and B of AB quartet, J=8.41 Hz, 2H), 7.64 (d, J=8.22 Hz, 1H), 7.56 (bd, J=8.02 Hz, 1H), 7.51 (bd, J=8.02 Hz, 1H), 7.29 (bd, J=7.63 Hz, 1H), 7.08 (bt, J=7.63 Hz, 1H), 5.29 (br s, 1H), 4.88 and 4.75 (A and B of AB quartet, J=15.65 Hz, 1H), 4.65 (br s, 1H), 4.23-4.16 (m, 1H), 4.16-4.08 (m, 1H), 4.06-3.98 (m, 2H), 3.92-3.65 (m, 3H), 3.03-2.70 (m, 4H), 2.52-2.41 (m, 3H), 2.26-2.18 (m, 1H), 2.21 (s, 1.5H), 2.16 (s, 1.5H), 2.16-2.08 (m, 2H), 1.66-1.44 (m, 2H).

Workup

  1. customThe solvent was then removed
  2. dissolutionthe crude product dissolved in MeOH
  3. filtrationThe solid was filtered off
  4. concentrationthe filtrate concentrated
  5. dissolutionThe crude piperidine was then dissolved in 4 mL EtOH
  6. customThe solvent was then removed by rotary evaporation
  7. customthe crude product was purified by column chromatography (silica, 0-10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-3fcf598f4f5048f483539d6f32ec9fd2
Source dataset
uspto-grants-2003_06
Patent number
US06583155B2

Reaction notes

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