Hydrochloric Acid → 1-(4-(2-(3-Phenoxy-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone dihydrochloride

HRID 335142Notes

Reaction equation

HRID 335142 reaction equation
[O:1]([C:8]1[C:9]([NH:24][C:25]2[S:26][CH:27]=[C:28]([CH:30]3[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]3)[N:29]=2)=[N:10][CH:11]=[C:12]([S:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[CH:21]=[CH:22][S:23][C:16]=23)[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:43]([Cl:46])(=[O:45])[CH3:44].C([O-])(O)=O.[Na+].[ClH:52]>C1COCC1>[ClH:46].[ClH:52].[O:1]([C:8]1[C:9]([NH:24][C:25]2[S:26][CH:27]=[C:28]([CH:30]3[CH2:35][CH2:34][N:33]([C:43](=[O:45])[CH3:44])[CH2:32][CH2:31]3)[N:29]=2)=[N:10][CH:11]=[C:12]([S:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]3[CH:21]=[CH:22][S:23][C:16]=23)[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 866314983-phenoxy-N-(4-(piperidin-4-yl)thiazol-2-yl)-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-amine

Product 1

HCID 250996511-(4-(2-(3-Phenoxy-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone dihydrochlorideYield 35.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 20 mL vial was charged with 3-phenoxy-N-(4-(piperidin-4-yl)thiazol-2-yl)-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-amine (80 mg, 0.15 mmol), triethylamine (0.043 mL, 0.31 mmol), and THF (2 mL). Acetyl chloride (0.011 mL, 0.15 mmol) was added and stirred at ambient temperature for 10 minutes. The reaction was poured into saturated aqueous NaHCO3 and extracted with EtOAc. The organic layer was dried with sodium sulfate, filtered and concentrated. The residue was purified on silica gel (5 to 10% methanol in EtOAc) to afford the title compound (35.1 mg, 35.9% yield) as a yellow solid after HCl salt formation. 1H NMR (d6-DMSO) δ 8.65 (d, 1H), 8.48 (d, 1H), 8.46 (d, 1H), 7.77 (d, 1H), 7.54 (d, 1H), 7.41 (m, 2H), 7.18 (m; 4H), 6.82 (s, 1H), 4.43 (m, 1H), 3.88 (m, 1H), 3.14 (m, 1H), 2.89 (m, 1H), 2.64 (m, 1H), 2.01 (s, 3H), 1.96 (m, 2H), 1.58 (m, 1H), 1.45 (m, 1H). Mass spectrum (apci) m/z=560.4 (M+H-2HCl).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic layer was dried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified on silica gel (5 to 10% methanol in EtOAc)

Sources & evidence

ORD record
ord-f49f6d7833464ebe8c16b235dc1f9668
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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