Trifluoroacetic acid → 4-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)benzoic acid

HRID 1410011Notes

Reaction equation

HRID 1410011 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:42]=[CH:41][S:40][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:26][C:27]4[CH:39]=[CH:38][C:30]([C:31]([O:33]C(C)(C)C)=[O:32])=[CH:29][CH:28]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:42]=[CH:41][S:40][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:26][C:27]4[CH:28]=[CH:29][C:30]([C:31]([OH:33])=[O:32])=[CH:38][CH:39]=4)=[O:25])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68379721Tert-butyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)benzoate

Product 1

HCID 665515444-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)benzoic acidYield 36.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)benzoate (75 mg, 0.127 mmol) in 5 mL of DCM was added TFA (2 mL) dropwise at room temperature. Then the reaction mixture was stirred at room temperature for 24 hours. The solvent was evaporated at 40° C. at reduced pressure and the residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 30% acetonitrile/70% water (0.1% TFA V/V) initially, and then proceed to 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxamido)benzoic acid (25 mg, 36.8%) as a white solid. 1H NMR (300 MHz, CD3OD): δ 8.71 (s, 1H), 7.99-7.96 (m, 2H), 7.68-7.65 (m, 2H), 7.51 (s, 1H), 7.27-7.23 (m, 1H), 6.86 (d, 1H, J=8.4 Hz), 3.79 (s, 3H), 3.70 (s, 3H), 2.67 (brs, 3H), 2.19-1.87 (m, 6H). LC-MS: 535 [M+H]+; 533 [M−H]−, tR=1.47 min. HPLC: 96.74% at 214 nm, 97.85% at 254 nm, tR=5.46 min.

Workup

  1. customThe solvent was evaporated at 40° C. at reduced pressure
  2. customthe residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm
  3. wait30% acetonitrile/70% water (0.1% TFA V/V) initially, and then proceed to 55% acetonitrile/45% water (0.1% TFA V/V) in a linear fashion after just 9 min.

Sources & evidence

ORD record
ord-e7bd8d935e314056beb5d82f5e182dd9
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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