Ammonium Chloride → 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 1809558Notes

Reaction equation

HRID 1809558 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[N:11]=[C:12]([NH:15][C:16]3[N:21]=[CH:20][C:19]([S:22]CCC(OC)=O)=[CH:18][C:17]=3[O:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[S:13][CH:14]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[Cl:36][C:37]1[CH:42]=[CH:41][N:40]=[C:39]2[CH:43]=[CH:44][S:45][C:38]=12.CC([O-])(C)C.[K+].[NH4+].[Cl-:53]>CS(C)=O>[ClH:36].[ClH:53].[O:29]([C:17]1[C:16]([NH:15][C:12]2[S:13][CH:14]=[C:10]([CH:7]3[CH2:6][CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8]3)[N:11]=2)=[N:21][CH:20]=[C:19]([S:22][C:37]2[CH:42]=[CH:41][N:40]=[C:39]3[CH:43]=[CH:44][S:45][C:38]=23)[CH:18]=1)[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 112752517-Chlorothieno[3,2-b]pyridineHCID 23665647Potassium tert-butoxideHCID 86631532Methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate

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 78%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of methyl 3-(6-(4-(1-acetylpiperidin-4-yl)thiazol-2-ylamino)-5-phenoxypyridin-3-ylthio)propanoate (20.2 g, 39.3 mmol) and 7-chlorothieno[3,2-b]pyridine (7.34 g, 43.3 mmol) in DMSO (500 mL) was purged with nitrogen for 30 minutes and then KOtBu (13.9 g, 118.0 mmol) was added and the reaction was stirred at ambient temperature for 2 hrs. The mixture was poured into saturated aqueous NH4Cl (1 L) and extracted with EtOAc (1 L). The organics were washed with water (3×500 mL), dried over Na2SO4 and concentrated to a residue that was purified on silica eluting with 3-5% MeOH/EtOAc. The purified free base was dissolved in CH2Cl2 (300 mL) and 1N HCl in Et2O (300 mL) was added the slurry was concentrated to dryness to afford 1-(4-(2-(3-phenoxy-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-ylamino)thiazol-4-yl)piperidin-1-yl)ethanone dihydrochloride (19.5 g, 78%) as a yellow solid which was dried in a high vacuum oven at 45° C. overnight. 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. customwas purged with nitrogen for 30 minutes
  2. extractionextracted with EtOAc (1 L)
  3. washThe organics were washed with water (3×500 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to a residue that
  6. customwas purified on silica eluting with 3-5% MeOH/EtOAc
  7. dissolutionThe purified free base was dissolved in CH2Cl2 (300 mL)
  8. addition1N HCl in Et2O (300 mL) was added the slurry
  9. concentrationwas concentrated to dryness

Sources & evidence

ORD record
ord-5666b02e1b7d458e98859e41eb258bc4
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

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