Trifluoroacetic acid → (7-Chloro-thieno[3,2-b]pyridin-2-yl)-(3-methoxy-azetidin-1-yl)-methanone

HRID 985292Notes

Reaction equation

HRID 985292 reaction equation
C([N:14]1[CH2:17][CH:16]([O:18][CH3:19])[CH2:15]1)(C1C=CC=CC=1)C1C=CC=CC=1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[Cl:34][C:35]1[CH:40]=[CH:39][N:38]=[C:37]2[CH:41]=[C:42]([C:44](Cl)=[O:45])[S:43][C:36]=12>C(Cl)Cl.[Pd].CCO>[Cl:34][C:35]1[CH:40]=[CH:39][N:38]=[C:37]2[CH:41]=[C:42]([C:44]([N:14]3[CH2:17][CH:16]([O:18][CH3:19])[CH2:15]3)=[O:45])[S:43][C:36]=12

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 5975241-Benzhydryl-3-methoxyazetidineHCID 221435437-Chlorothieno[3,2-b]pyridine-2-carbonyl chloride

Product 1

HCID 22143554(7-Chloro-thieno[3,2-b]pyridin-2-yl)-(3-methoxy-azetidin-1-yl)-methanoneYield 56%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A 100 ml round bottom flask was charged with 1-benzhydryl-3-methoxy-azetidine 78a (447 mg, 1.77 mmole), 10% Pd/C (300 mg), trifluoroacetic acid (0.15 ml, 1.94 mmole) and EtOH (30 ml) and placed under 1 atm H2 and vigorously stirred at rt. After 2 hr, the catalyst was removed and washed with MeOH. The filtrate was concentrated under reduced pressure to give the crude azetidine which was dissolved in CH2Cl2. To this solution were added triethylamine (0.6 ml, 4.41 mmole) and 7-chloro-thieno[3,2-b]pyridine-2-carbonyl chloride, prepared as previously described in example 25a. After stirring at ambient temperature overnight, the reaction mixture was diluted with more CH2Cl2, then washed sequentially with 0.5N HCl, satd. NaHCO3 (aq), and brine. The organic layer was dried (MgSO4) and concentrated to near dryness under reduced pressure, then triturated with hexanes to give 278 mg (56%) of the desired product as a light yellow solid. 1H NMR (DMSO-d6) δ8.73(1H, d, J=5.1 Hz), 8.00 (1H, s), 7.70 (1H, d, J=5.1 Hz), 4.77 (1H, m), 4.49 (1H, m), 4.31 (2H, m), 3.90 (1H, m), 3.24 (3H, s). APCI m/z 283/285 (M+H)+.

Workup

  1. customthe catalyst was removed
  2. washwashed with MeOH
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto give the crude azetidine which
  5. customprepared
  6. stirringAfter stirring at ambient temperature overnight
  7. washwashed sequentially with 0.5N HCl
  8. dry with materialThe organic layer was dried (MgSO4)
  9. concentrationconcentrated
  10. customtriturated with hexanes

Sources & evidence

ORD record
ord-08c602fd5d484110b7200c82f528e552
Source dataset
uspto-grants-2005_03
Patent number
US06869962B2

Reaction notes

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