Pyridine → 4-Hydroxymethylpiperidine-1-carboxylic acid [7-methoxy-4-(tetrahydro-pyran-4-yl)-thiazolo[5,4-c]pyridin-2-yl]-amide

HRID 917482Notes

Reaction equation

HRID 917482 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:17]=[C:16]([NH2:18])[S:15][C:5]=2[C:6]([CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[N:7][CH:8]=1.N1C=CC=CC=1.Cl[C:26](OC1C=CC=CC=1)=[O:27].[OH:35][CH2:36][CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>ClCCl.O1CCCC1>[CH3:1][O:2][C:3]1[C:4]2[N:17]=[C:16]([NH:18][C:26]([N:40]3[CH2:41][CH2:42][CH:37]([CH2:36][OH:35])[CH2:38][CH2:39]3)=[O:27])[S:15][C:5]=2[C:6]([CH:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)=[N:7][CH:8]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 4207714-PiperidinemethanolHCID 860384927-Methoxy-4-(tetrahydro-pyran-4-yl)thiazolo[5,4-c]pyridin-2-ylamine

Product 1

HCID 865972844-Hydroxymethylpiperidine-1-carboxylic acid [7-methoxy-4-(tetrahydro-pyran-4-yl)-thiazolo[5,4-c]pyridin-2-yl]-amideYield 45.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 17 mg (0.06 mmol) 7-methoxy-4-(tetrahydro-pyran-4-yl)-thiazolo[5,4-c]pyridin-2-ylamine and 0.015 ml (0.19 mmol) pyridine in 1.5 ml dichloromethane and 0.5 ml tetrahydrofuran was added 0.009 ml (0.07 mmol) phenyl chloroformate and stirring continued at 50° C. for 1 h. 37 mg (0.32 mmol) 4-(hydroxymethyl)piperidine was then added and stirring continued at 50° C. for a further 1 h. The reaction mixture was then concentrated in vacuo. Flash chromatography (methanol/dichloromethane 1/40 then 1/20) afforded 11 mg (42%) 4-hydroxymethylpiperidine-1-carboxylic acid [7-methoxy-4-(tetrahydro-pyran-4-yl)-thiazolo[5,4-c]pyridin-2-yl]-amide as a white crystalline solid. ES-MS m/e (%): 407 (M+H+, 100).

Workup

  1. stirringstirring
  2. waitcontinued at 50° C. for a further 1 h
  3. concentrationThe reaction mixture was then concentrated in vacuo

Sources & evidence

ORD record
ord-f681fe1d7af5460d89f45aa5a4b307eb
Source dataset
uspto-grants-2007_09
Patent number
US07273865B2

Reaction notes

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