Trifluoroacetic acid → HCID 67250086, compound

HRID 410645Notes

Reaction equation

HRID 410645 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[C:7]([NH:21][C:22]2[N:27]=[C:26]([O:28][CH:29]3[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30]3)[CH:25]=[CH:24][N:23]=2)[CH:8]=[C:9]([C:11]2[S:15][C:14]([C:16]3([OH:20])[CH2:19][CH2:18][CH2:17]3)=[N:13][CH:12]=2)[CH:10]=1)(=[O:3])[CH3:2].C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[OH:20][C:16]1([C:14]2[S:15][C:11]([C:9]3[CH:10]=[C:5]([NH:4][C:1](=[O:3])[CH3:2])[CH:6]=[C:7]([NH:21][C:22]4[N:27]=[C:26]([O:28][CH:29]5[CH2:30][CH2:31][NH:32][CH2:33][CH2:34]5)[CH:25]=[CH:24][N:23]=4)[CH:8]=3)=[CH:12][N:13]=2)[CH2:19][CH2:18][CH2:17]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 67432798Tert-butyl 4-{[2-({3-(acetylamino)-5-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]phenyl}amino)pyrimidin-4-yl]oxy}piperidine-1-carboxylate

Product 1

HCID 67250086HCID 67250086, compoundYield 91,176.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the product of Step 4 (20 mg, 0.034 mmol) in DCM (1 mL) was added TFA (133 μL, 1.722 mmol). The mixture was stirred at ambient temperature for 1 hr. LCMS indicated complete reaction. To the reaction was added saturated aqueous NaHCO3 to adjust pH>8 and the product was extracted with ethyl acetate, The combined organic layer was dried, filtered and solvent removed in vacuo to afford 15 mg (0.031 mol, 91%) of N-(3-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-5-{[4-(piperidin-4-yloxy)pyrimidin-2-yl]amino}phenyl)acetamide as pale yellow oil. MS ESI: [M+H]+ m/z 481.2. 1H NMR (600 MHz, CD3OD): δ 8.16 (m, 2H); 7.90 (s, 1H); 7.55 (s, 1H); 7.30 (s, 1H); 6.26 (d, J=5.4 Hz, 1H); 5.58 (m, 1H); 3.34 (m, 2H); 3.21 (m, 2H); 2.65 (m, 2H); 2.40 (m, 2H); 2.22 (m, 2H); 2.14 (s, 3H); 2.01 (m, 4H). rhSYK activity=+++

Workup

  1. customreaction
  2. extractionthe product was extracted with ethyl acetate
  3. customThe combined organic layer was dried
  4. filtrationfiltered
  5. customsolvent removed in vacuo

Sources & evidence

ORD record
ord-9b5c0196ed604add943b4569caa51fe7
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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