Piperidine → 2-(2-Piperidin-1-ylmethyl-1H-indol-6-yloxy)-thiazolo[4,5-b]pyridine

HRID 1947523Notes

Reaction equation

HRID 1947523 reaction equation
[S:1]1[C:9]2[C:4](=[N:5][CH:6]=[CH:7][CH:8]=2)[N:3]=[C:2]1[O:10][C:11]1[CH:19]=[C:18]2[C:14]([CH:15]=[C:16]([CH:20]=O)[NH:17]2)=[CH:13][CH:12]=1.[NH:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[N:22]1([CH2:20][C:16]2[NH:17][C:18]3[C:14]([CH:15]=2)=[CH:13][CH:12]=[C:11]([O:10][C:2]2[S:1][C:9]4[C:4]([N:3]=2)=[N:5][CH:6]=[CH:7][CH:8]=4)[CH:19]=3)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 8082PiperidineHCID 5049666Sodium triacetoxyborohydrideHCID 595776126-(Thiazolo[4,5-b]pyridin-2-yloxy)-1H-indole-2-carbaldehyde

Product 1

HCID 498328182-(2-Piperidin-1-ylmethyl-1H-indol-6-yloxy)-thiazolo[4,5-b]pyridineYield 13%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 6-(thiazolo[4,5-b]pyridin-2-yloxy)-1H-indole-2-carbaldehyde (76 mg, 0.26 mmol) in DCM (3 mL) was added piperidine (0.05 mL, 43 mg, 0.51 mmol), Na(OAc)3BH (65 mg, 0.31 mmol) and the reaction mixture was stirred (rt, 12 h). The reaction mixture was partitioned between saturated NaHCO3 (10 ml) and DCM (20 mL). The organic layer was separated and the aqueous layer was extracted with DCM (2×25 mL). The organic layer was dried, filtered and concentrated in vacuo. The resulting residue was purified by reverse phase HPLC to provide the title compound as a colorless solid (12 mg, 13%). MS (ESI): mass calcd. for C20H20N4OS, 364.1; m/z found, 365.1 [M+H]+. 1H NMR (500 MHz, CDCl3/CD3OD, 10/1): 8.51 (d, J=4.8, 1H), 7.97 (d, J=7.9, 1H), 7.54 (d, J=8.5, 1H), 7.40 (s, 1H), 7.18 (dd, J=7.9, 4.9, 1H), 7.02 (d, J=8.5, 1H), 6.36 (s, 1H), 3.63 (s, 2H), 2.53-2.47 (m, 2H), 2.47-2.36 (m, 2H), 1.76-1.44 (m, 6H).

Workup

  1. customThe reaction mixture was partitioned between saturated NaHCO3 (10 ml) and DCM (20 mL)
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with DCM (2×25 mL)
  4. customThe organic layer was dried
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-51f9dc061c83410fa3ec6629f9e9c57d
Source dataset
uspto-grants-2013_03
Patent number
US08399465B2

Reaction notes

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