1,2-Dichloroethane → 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(pyridin-4-yl)ethyl)piperidine-3-carboxamide

HRID 1410044Notes

Reaction equation

HRID 1410044 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([OH:26])=O)[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[N:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][NH2:38])=[CH:32][CH:31]=1.C(Cl)CCl.CN1C=CN=C1>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[C:13]3[N:29]=[CH:28][S:27][C:14]=3[N:15]=[C:16]([N:18]3[CH2:23][CH2:22][CH2:21][CH:20]([C:24]([NH:38][CH2:37][CH2:36][C:33]4[CH:34]=[CH:35][N:30]=[CH:31][CH:32]=4)=[O:26])[CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 13901-MethylimidazoleHCID 832754-PyridineethanamineHCID 683795141-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid

Product 1

HCID 665489601-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(pyridin-4-yl)ethyl)piperidine-3-carboxamideYield 40.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The mixture of 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-3-carboxylic acid (50 mg, 0.12 mmol), 2-(pyridin-4-yl)ethanamine (50 mg, 0.41 mmol), EDC (50 mg, 0.26 mmol) and 1-methyl-1H-imidazole (50 mg, 0.61 mmol) in 25 mL of DCM was stirred at room temperature overnight. Excess of DCM was removed under reduced pressure and the residue was purified by silica gel chromatography, eluting with petroleum ether and ethyl acetate (3:1) to give 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(pyridin-4-yl)ethyl)piperidine-3-carboxamide (25 mg, 39%) as a yellow sold. 1H NMR (300 MHz, DMSO): δ 9.64 (s, 1H), 8.85 (s, 1H), 8.46-8.44 (m, 2H), 8.02-8.01 (m, 1H), 7.71-7.69 (m, 1H), 7.33-7.21 (m, 3H), 6.92 (d, 1H, J=9.0 Hz), 4.64-4.63 (m, 2H), 3.75 (s, 3H), 3.73 (s, 3H), 3.35-3.30 (m, 2H), 2.98-2.91 (m, 2H), 2.77-2.75 (m, 2H), 2.51 (brs, 1H), 1.82-1.42 (m, 4H). LC-MS: 520 [M+H]+, 260 [M/2+H]+, 518 [M−H]−, tR=1.29 min. HPLC: 97.55% at 214 nm, 97.72% at 254 nm, tR=3.51 min.

Workup

  1. customExcess of DCM was removed under reduced pressure
  2. customthe residue was purified by silica gel chromatography
  3. washeluting with petroleum ether and ethyl acetate (3:1)

Sources & evidence

ORD record
ord-91c6c158ac594564b561f5175af83557
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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