Triethylamine → {5-[2-(6-Cyano-thieno[3,2-b]pyridin-7-ylamino)-ethyl]-thiazol-2-yl}-carbamic acid tert-butyl ester

HRID 1468994Notes

Reaction equation

HRID 1468994 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]2[CH:10]=[CH:11][S:12][C:3]=12.[C:13]([O:17][C:18](=[O:28])[NH:19][C:20]1[S:21][C:22]([CH2:25][CH2:26][NH2:27])=[CH:23][N:24]=1)([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C>C(O)C>[C:13]([O:17][C:18](=[O:28])[NH:19][C:20]1[S:21][C:22]([CH2:25][CH2:26][NH:27][C:2]2[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]3[CH:10]=[CH:11][S:12][C:3]=23)=[CH:23][N:24]=1)([CH3:16])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 118164017-Chlorothieno[3,2-b]pyridine-6-carbonitrileHCID 45117855tert-Butyl (5-(2-aminoethyl)thiazol-2-yl)carbamate

Product 1

HCID 86640519{5-[2-(6-Cyano-thieno[3,2-b]pyridin-7-ylamino)-ethyl]-thiazol-2-yl}-carbamic acid tert-butyl esterYield 40.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred mixture of 7-chloro-thieno[3,2-b]pyridine-6-carbonitrile (47.8 mg, 0.25 mmol), [5-(2-amino-ethyl)-thiazol-2-yl]-carbamic acid tert-butyl ester (J Med Chem, 1992, 35, 3239-3246) (54.6 mg, 0.22 mmol), and triethylamine (0.04 ml, 0.28 mmol) in 3 ml of ethanol was heated to reflux for 17 hr. Ethanol was evaporated, and the residue was partitioned between dichloromethane and aqueous NaHCO3. The organic layer was washed with H2O, dried over MgSO4, filtered, and concentrated in vacuum. The resulting residue was purified by silica gel chromatography (MeOH/CH2Cl2/NH3=1/20/0.1) to give 36.1 mg (40%) of yellow solid. 1H NMR (300 MHz, CDCl3) δ 8.49 (s, 1H), 7.82 (d, J=5.4 Hz, 1H), 7.52 (d, J=5.4 Hz, 1H), 7.18 (s, 1H), 5.32 (m, 1H), 4.08 (q, J=7.2 Hz, 2H), 3.20 (t, J=7.2 Hz, 2H), 1.55 (s, 9H); LC-MS (ESI) m/z 402.1 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 17 hr
  3. customEthanol was evaporated
  4. customthe residue was partitioned between dichloromethane and aqueous NaHCO3
  5. washThe organic layer was washed with H2O
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuum
  9. customThe resulting residue was purified by silica gel chromatography (MeOH/CH2Cl2/NH3=1/20/0.1)

Sources & evidence

ORD record
ord-cf9f033e07074747bbf4f21986e2485f
Source dataset
uspto-grants-2015_04
Patent number
US09006252B2

Reaction notes

Loading…