Pyridine → 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-N-(4-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

HRID 1011788Notes

Reaction equation

HRID 1011788 reaction equation
ClC(N(C)C)=C(C)C.[N:9]1([C:13]([C:15]2[CH:16]=[C:17]([Cl:37])[C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@H:32]4[CH2:36][CH2:35][O:34][CH2:33]4)[CH:30]=3)[C:25]([OH:27])=O)=[N:19][CH:20]=2)=[O:14])[CH2:12][CH2:11][CH2:10]1.[NH2:38][C:39]1[S:40][CH:41]=[C:42]([CH3:44])[N:43]=1.N1C=CC=CC=1>C(Cl)Cl>[N:9]1([C:13]([C:15]2[CH:16]=[C:17]([Cl:37])[C:18]([O:21][C:22]3[CH:23]=[C:24]([CH:28]=[C:29]([O:31][C@H:32]4[CH2:36][CH2:35][O:34][CH2:33]4)[CH:30]=3)[C:25]([NH:38][C:39]3[S:40][CH:41]=[C:42]([CH3:44])[N:43]=3)=[O:27])=[N:19][CH:20]=2)=[O:14])[CH2:10][CH2:11][CH2:12]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 741432-Amino-4-methylthiazoleHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 536296753-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid

Product 1

HCID 160400043-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-N-(4-methyl-1,3-thiazol-2-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamideYield 31.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-Chloro-N,N,2-trimethyl-1-propenylamine (0.70 mL, 0.53 mmol) was added to a solution of 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-[(3S)-tetrahydrofuran-3-yloxy]benzoic acid (200 mg, 0.48 mmol) in DCM (6 mL) and stirred at RT for 2 hours. 2-Amino-4-methylthiazole (110 mg, 0.96 mmol) and pyridine (0.078 mL, 0.96 mmol) were added and the reaction stirred at RT for 16 hours. The solvent was removed in vacuo, water (20 mL) added and the mixture extracted with ethyl acetate (3×20 mL). The extracts were combined and washed with 2N hydrochloric acid (20 mL), saturated aqueous sodium bicarbonate solution (20 mL), water (20 mL), brine (20 mL), dried (MgSO4), filtered, and evaporated in vacuo. The residue was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (78 mg).

Workup

  1. stirringthe reaction stirred at RT for 16 hours
  2. customThe solvent was removed in vacuo, water (20 mL)
  3. additionadded
  4. extractionthe mixture extracted with ethyl acetate (3×20 mL)
  5. washwashed with 2N hydrochloric acid (20 mL), saturated aqueous sodium bicarbonate solution (20 mL), water (20 mL), brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was chromatographed on silica
  10. washeluting with a gradient of 50-100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-4ac44add58bc42cba7764885eca00b6c
Source dataset
uspto-grants-2011_07
Patent number
US07977328B2

Reaction notes

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