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

HRID 1410036Notes

Reaction equation

HRID 1410036 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][CH:21]([C:24]([OH:26])=O)[CH2:20][CH2:19]3)[N:17]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].Br.[NH2:31][CH2:32][CH2:33][C:34]1[CH:39]=[CH:38][NH:37][C:36](=[O:40])[CH:35]=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[CH2:19][CH2:20][CH:21]([C:24]([NH:31][CH2:32][CH2:33][C:34]4[CH:39]=[CH:38][NH:37][C:36](=[O:40])[CH:35]=4)=[O:26])[CH2:22][CH2:23]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 683790841-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-4-carboxylic acidHCID 683793994-(2-aminoethyl)pyridin-2(1H)-one hydrobromide

Product 1

HCID 665489571-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(2-oxo-1,2-dihydropyridin-4-yl)ethyl)piperidine-4-carboxamideYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The mixture of 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-4-carboxylic acid (70 mg, 0.22 mmol), 4-(2-aminoethyl)pyridin-2(1H)-one hydrobromide (70 mg, 0.32 mmol), EDC (170 mg, 0.89 mmol) and 1-methyl-1H-imidazole (108 mg, 1.32 mmol) in 20 mL of DCM was stirred at room temperature overnight. Excess of DCM was removed under reduced pressure and the residue was triturated with H2O (30 mL) and EtOAc (20 mL) then dried under reduce pressure to give 1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)-N-(2-(2-oxo-1,2-dihydropyridin-4-yl)ethyl)piperidine-4-carboxamide (25 mg, 40%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.62 (s, 1H), 7.61 (d, 1H, J=2.4 Hz), 7.35 (d, 1H, J=7.2 Hz), 7.20 (dd, 1H, J1=8.7 Hz, J2=2.4 Hz), 6.95 (d, 1H, J=8.7 Hz), 6.36-6.32 (m, 2H), 4.83-4.79 (m, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 3.44 (t, 2H, J=6.8 Hz), 3.00-2.92 (m, 2H), 2.70 (t, 2H, J=6.8 Hz), 2.45 (brs, 1H), 1.80-1.64 (m, 4H). LC-MS: 536 [M+H]+, 534 [M−H]−, tR=1.38 min. HPLC: 95.70% at 214 nm, 96.10% at 254 nm, tR=3.65 min.

Workup

  1. customExcess of DCM was removed under reduced pressure
  2. customthe residue was triturated with H2O (30 mL) and EtOAc (20 mL)
  3. customthen dried

Sources & evidence

ORD record
ord-d2a095932b504e44bb082cbc2c483df8
Source dataset
uspto-grants-2014_12
Patent number
US08921383B2

Reaction notes

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