tert-butyl 4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate → Tert-butyl 4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)piperidine-1-carboxylate

HRID 1676363Notes

Reaction equation

HRID 1676363 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:31])[CH:3]=1.[H][H]>[Pd].CO>[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([CH:16]4[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH2:18][CH2:17]4)[S:15][C:8]=23)=[C:4]([F:31])[CH:3]=1

Participants

5

Reactant 2

HCID 59684980tert-butyl 4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 67346565Tert-butyl 4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)piperidine-1-carboxylateYield 98.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A round-bottomed flask was charged with tert-butyl 4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl) -5,6-dihydropyridine-1(2H)-carboxylate (Example 149, Step A, 146.3 mg, 0.3314 mmol), palladium on carbon (117.7 mg, 0.099 mmol, 10%) and MeOH (10 mL). The air was exchanged with nitrogen three times and then was exchanged with hydrogen another three times. Then the reaction mixture was stirred under hydrogen at room temperature until the starting material had been consumed (2 hours). The mixture was filtered to remove the palladium on carbon and then the solvent was removed under reduced pressure to afford crude product. The crude product was purified by silica gel chromatography (dichloromethane/7 M NH3 in MeOH from 100/1 to 10/1, v/v) to afford product (144.5 mg, 98.3%). LRMS (APCI pos): >95% purity, 254 nm, m/e 444 (M+1). 1H NMR (400 MHz, CD3Cl) δ 8.41 (d, 1H), 7.27 (m, 1H), 7.02 (t, 1H), 6.54 (dd, 1H), 6.46 (m, 2H), 4.24 (m, 2H), 3.84 (br s, 2H), 3.07 (m, 1H), 2.88 (m, 2H), 2.09 (m, 2H), 1.74 (m, 2H), 1.49 (s, 9H).

Workup

  1. customhad been consumed (2 hours)
  2. filtrationThe mixture was filtered
  3. customto remove the palladium on carbon
  4. customthe solvent was removed under reduced pressure
  5. customto afford crude product
  6. customThe crude product was purified by silica gel chromatography (dichloromethane/7 M NH3 in MeOH from 100/1 to 10/1

Sources & evidence

ORD record
ord-c7f3938e67a3474590e92fd0d037114c
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

Loading…