7-Chlorothieno[3,2-b]pyridine → tert-butyl 4-((2-(3-phenoxy-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-Ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate

HRID 1806189Notes

Reaction equation

HRID 1806189 reaction equation
CC([O-])(C)C.[K+].Cl[C:8]1[CH:13]=[CH:12][N:11]=[C:10]2[CH:14]=[CH:15][S:16][C:9]=12.COC(=O)CC[S:22][C:23]1[CH:24]=[C:25]([O:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:26]([NH:29][C:30]2[S:31][CH:32]=[C:33]([CH2:35][CH:36]3[CH2:41][CH2:40][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:38][CH2:37]3)[N:34]=2)=[N:27][CH:28]=1>CS(C)=O>[O:49]([C:25]1[C:26]([NH:29][C:30]2[S:31][CH:32]=[C:33]([CH2:35][CH:36]3[CH2:37][CH2:38][N:39]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:40][CH2:41]3)[N:34]=2)=[N:27][CH:28]=[C:23]([S:22][C:8]2[CH:13]=[CH:12][N:11]=[C:10]3[CH:14]=[CH:15][S:16][C:9]=23)[CH:24]=1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

Participants

5

Reactant 3

HCID 112752517-Chlorothieno[3,2-b]pyridineHCID 23665647Potassium tert-butoxideHCID 57742831Tert-butyl 4-((2-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate

Product 1

HCID 57742604tert-butyl 4-((2-(3-phenoxy-5-(thieno[3,2-b]pyridin-7-ylthio)pyridin-2-Ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylateYield 97.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

Added potassium 2-methylpropan-2-olate (0.443 g, 3.95 mmol) to a solution of 7-chlorothieno[3,2-b]pyridine (0.268 g, 1.58 mmol) and tert-butyl 4-((2-(5-(3-methoxy-3-oxopropylthio)-3-phenoxypyridin-2-ylamino)thiazol-4-yl)methyl)piperidine-1-carboxylate (0.77 g, 1.32 mmol) in DMSO (8 mL). The reaction was stirred for two hours, then set aside to react at ambient temperature for 60 hours. The reaction was partitioned between ethyl acetate and saturated ammonium chloride. Washed the organic layer twice with water and brine, dried, and concentrated. The residue was purified by MPLC (Biotage) eluting with 1:1 hexane:ethyl acetate. The major UV active component with an Rf of 0.3 was collected and concentrated to afford the title compound (0.810 g, 97.4% yield) as a white powder: 1H NMR (CDCl3) δ 8.88 (s, 1H), 8.46 (d, 1H), 8.32 (s, 1H), 7.72 (d, 1H), 7.54 (d, 1H), 7.38 (t, 2H), 7.20 (t, 1H), 7.18 (s, 1H), 7.04 (d, 2H), 6.73 (d, 1H), 6.51 (s, 1H), 4.09 (m, 2H), 2.68 (m, 2H), 2.59 (d, 2H), 1.87 (m, 1H), 1.66 (m, 2H), 1.45 (s, 9H), 1.16 (m, 2H).

Workup

  1. customto react at ambient temperature for 60 hours
  2. customThe reaction was partitioned between ethyl acetate and saturated ammonium chloride
  3. washWashed the organic layer twice with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by MPLC (Biotage)
  7. washeluting with 1:1 hexane
  8. customThe major UV active component with an Rf of 0.3 was collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-da93d6a33c7946a989a15db16f76daee
Source dataset
uspto-grants-2013_01
Patent number
US08354540B2

Reaction notes

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