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

HRID 1410097Notes

Reaction equation

HRID 1410097 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:41]=[CH:40][S:39][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([C:23]([NH:25][C:26]4[CH:38]=[CH:37][C:29]([C:30]([O:32]C(C)(C)C)=[O:31])=[CH:28][CH:27]=4)=[O:24])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:41]=[CH:40][S:39][C:14]=3[N:15]=[C:16]([N:18]3[CH2:22][CH2:21][CH:20]([C:23]([NH:25][C:26]4[CH:27]=[CH:28][C:29]([C:30]([OH:32])=[O:31])=[CH:37][CH:38]=4)=[O:24])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68379487Tert-butyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidine-3-carboxamido)benzoate

Product 1

HCID 665501174-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidine-3-carboxamido)benzoic acidYield 59.8%

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)pyrrolidine-3-carboxamido)benzoate (105 mg, 0.18 mmol) in 10 mL of dichloromethane was added trifluoroacetic acid (5 mL) in one portion at room temperature. Then the reaction mixture was stirred at this temperature for 24 hours. The solvent was evaporated at 37° 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 60% acetonitrile/40% 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)pyrrolidine-3-carboxamido)benzoic acid (56 mg, 59%) as a white solid. 1H NMR (300 MHz, DMSO): δ 10.42 (s, 1H), 9.64 (s, 1H), 8.84 (s, 1H), 7.92-7.73 (m, 6H), 7.48 (brs, 1H), 6.93 (d, 1H, J=9.0 Hz), 3.92-3.36 (m, 11H), 2.29-2.21 (m, 2H). LC-MS: 521 [M+H]+, tR=1.38 min. HPLC: 99.34% at 214 nm, 99.25% at 254 nm, tR=4.75 min.

Workup

  1. customThe solvent was evaporated at 37° 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 60% acetonitrile/40% water (0.1% TFA V/V) in a linear fashion after just 9 min.

Sources & evidence

ORD record
ord-f094c9f3a6f349f7bd9e9f7757b680f8
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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