Hydrochloric Acid → N-(4-methylthiazol-2-yl)-3-(phenylthio)-5-((tetrahydropyran-4-ylidene)methyl)pyridin-2-amine hydrochloride

HRID 1806060Notes

Reaction equation

HRID 1806060 reaction equation
[ClH:1].[CH3:2][C:3]1[N:4]=[C:5]([NH:8][C:9]2[N:14]=[CH:13][C:12]([CH:15]([CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)O)=[CH:11][C:10]=2[S:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[S:6][CH:7]=1.O.CC1C=CC(S(O)(=O)=O)=CC=1.Cl>C1(C)C=CC=CC=1>[ClH:1].[CH3:2][C:3]1[N:4]=[C:5]([NH:8][C:9]2[C:10]([S:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:11][C:12]([CH:15]=[C:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[CH:13][N:14]=2)[S:6][CH:7]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 521998p-Toluenesulfonic acid monohydrateHCID 86631490(6-(4-methylthiazol-2-ylamino)-5-(phenylthio)Pyridin-3-yl)(tetrahydro-2H-pyran-4-yl)methanol hydrochloride

Product 1

HCID 86631492N-(4-methylthiazol-2-yl)-3-(phenylthio)-5-((tetrahydropyran-4-ylidene)methyl)pyridin-2-amine hydrochlorideYield 35%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A 10 mL round-bottomed flask was charged with (6-(4-methylthiazol-2-ylamino)-5-(phenylthio)pyridin-3-yl)(tetrahydro-2H-pyran-4-yl)methanol hydrochloride (125 mg, 0.278 mmol), 4-methylbenzenesulfonic acid hydrate (5.28 mg, 0.0278 mmol), Toluene (5 mL) and heated to reflux in dean stark trap for 24 7 hours. The reaction was cooled to ambient temperature and partitioned between saturated aqueous sodium bicarbonate and CH2Cl2. The organic layer was dried with sodium sulfate, filtered and concentrated. The residue was purified on silica gel (25% EtOAc in hexanes) to afford the title compound (42 mg, 35.0% yield) as after HCl salt formation. 1H NMR (CDCl3) δ 12.24 (bs, 1H), 8.18 (m, 1H), 7.71 (m, 1H), 7.54 (m, 2H), 7.30 (m, 3H), 6.40 (s, 1H), 6.20 (s, 1H), 3.78 (t, 2H), 3.65 (t, 2H), 2.45 (s, 3H), 2.42 (m, 4H). Mass spectrum (apci) m/z=396.2 (M+H—HCl).

Workup

  1. temperatureheated
  2. temperatureto reflux in dean stark trap for 24 7 hours
  3. custompartitioned between saturated aqueous sodium bicarbonate and CH2Cl2
  4. dry with materialThe organic layer was dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel (25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-99d1ce64421c438f80f73aae253f1315
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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