Hydrochloric Acid → 2-(5-{3-[(4-Cyclopropyl-5-fluoropyrimidin-2-yl)-amino]-5-fluorophenyl}-1,3-thiazol-2-yl)propane-1,2-diol

HRID 410572Notes

Reaction equation

HRID 410572 reaction equation
[Si]([O:8][CH2:9][C:10]([C:13]1[S:14][C:15]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([NH:25][C:26]3[N:31]=[C:30]([CH:32]4[CH2:34][CH2:33]4)[C:29]([F:35])=[CH:28][N:27]=3)[CH:19]=2)=[CH:16][N:17]=1)([OH:12])[CH3:11])(C(C)(C)C)(C)C.Cl>CO>[CH:32]1([C:30]2[C:29]([F:35])=[CH:28][N:27]=[C:26]([NH:25][C:20]3[CH:19]=[C:18]([C:15]4[S:14][C:13]([C:10]([OH:12])([CH3:11])[CH2:9][OH:8])=[N:17][CH:16]=4)[CH:23]=[C:22]([F:24])[CH:21]=3)[N:31]=2)[CH2:33][CH2:34]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 672611911-{[Tert-butyl(dimethyl)silyl]oxy}-2-(5-{3-[(4-cyclopropyl-5-fluoropyrimidin-2-yl)amino]-5-fluorophenyl}-1,3-thiazol-2-yl)propan-2-ol

Product 1

HCID 584561652-(5-{3-[(4-Cyclopropyl-5-fluoropyrimidin-2-yl)-amino]-5-fluorophenyl}-1,3-thiazol-2-yl)propane-1,2-diolYield 83%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the product of Step 5 (150 mg, 0.289 mmol) in methanol (4 mL) was added HCl (4.0 M in dioxane) (0.072 mL, 0.289 mmol). After 30 minutes, the reaction mixture was concentrated. The residue was purified by preparative HPLC Reverse phase (C-18), eluting with acetonitrile/water+0.05% TFA to give 2-(5-{3-[(4-cyclopropyl-5-fluoropyrimidin-2-yl)-amino]-5-fluorophenyl}-1,3-thiazol-2-yl)propane-1,2-diol (95 mg, 0.24 mmol, 81%). MS ESI: [M+H]+ m/z 405.1. 1H NMR (600 MHz, DMSO-d6) δ9.83 (s, 1H); 8.41 (s, 1H); 8.01 (s, 1H); 7.75 (s, 1H); 7.53 (d, J=11.4 Hz, 1H); 7.06 (d, J=9.6 Hz, 1H); 5.89 (s, 1H); 4.89 (s, 1H); 3.52 (s, 2H); 2.29-2.22 (m, 1H); 1.43 (s, 3H); 1.20-1.12 (m, 4H). rhSYK activity=+++

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customThe residue was purified by preparative HPLC Reverse phase (C-18)
  3. washeluting with acetonitrile/water+0.05% TFA

Sources & evidence

ORD record
ord-cb67f0b55b5e4a3e98c08f66e81c55bc
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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