Hydrochloric Acid → HCID 58456275, compound

HRID 1040210Notes

Reaction equation

HRID 1040210 reaction equation
[Si]([O:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]2[CH:20]=[C:21]([C:26]3[S:30][C:29]([C:31]4([OH:39])[CH2:36][O:35]C(C)(C)[O:33][CH2:32]4)=[N:28][CH:27]=3)[CH:22]=[C:23]([CH3:25])[CH:24]=2)[N:13]=1)(C(C)(C)C)(C)C.Cl>O1CCCC1.CO>[OH:8][CH2:9][CH2:10][O:11][C:12]1[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]2[CH:20]=[C:21]([C:26]3[S:30][C:29]([C:31]([OH:39])([CH2:36][OH:35])[CH2:32][OH:33])=[N:28][CH:27]=3)[CH:22]=[C:23]([CH3:25])[CH:24]=2)[N:13]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 674315445-[5-(3-{[4-(2-{[Tert-butyl(dimethyl)silyl]oxy}ethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-2,2-dimethyl-1,3-dioxan-5-ol

Product 1

HCID 58456275HCID 58456275, compoundYield 56.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-[5-(3-{[4-(2-{[tert-butyl(dimethyl)silyl]oxy}ethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]-2,2-dimethyl-1,3-dioxan-5-ol (185 mg, 0.32 mmol) in tetrahydrofuran (1.6 mL) was added hydrochloric acid (1.0 N, 970 μL, 0.97 mmol) at room temperature. The mixture was stirred at room temperature for 2.5 h, then diluted with methanol, filtered, and purified by reverse phase HPLC (10:90 to 90:10 acetonitrile:water with a 0.1% trifluoroacetic acid modifier). The combined fractions were dried on a lyophilizer, dissolved in methanol, and the TEA salt converted to the free base using StratoSpheres SPE PL-HCO3 MP-Resin (0.9 mmol) cartridges to give 2-[5-(3-{[4-(2-hydroxyethoxy)pyrimidin-2-yl]amino}-5-methylphenyl)-1,3-thiazol-2-yl]propane-1,2,3-triol (75 mg, 0.18 mmol, 56% yield) as a white foam. MS ESI: [M+H]+ m/z 419.1. 1H NMR (500 MHz, DMSO-d6) δ 9.65 (dd, J=4.3, 15.1, 1H), 8.21 (d, J=5.7, 1H), 7.96 (s, 1H), 7.90 (s, 1H), 7.47 (s, 1H), 7.09 (s, 1H), 6.31 (s, 1H), 4.39 (s, 2H), 3.79-3.72 (m, 2H), 3.72-3.63 (m, 4H), 2.30 (s, 3H). rhSYK activity=+++

Workup

  1. filtrationfiltered
  2. custompurified by reverse phase HPLC (10:90 to 90:10 acetonitrile
  3. customThe combined fractions were dried on a lyophilizer
  4. dissolutiondissolved in methanol

Sources & evidence

ORD record
ord-61b3699ff83e49829f5d27d1596337fe
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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