Benzenesulfonyl chloride → ethyl (3-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamate

HRID 2178385Notes

Reaction equation

HRID 2178385 reaction equation
[CH:1]1([CH:4]([C:29]2[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=2)[O:5][C:6]2[CH:26]=[CH:25][C:9]([CH2:10][NH:11][C:12]3[C:17]([NH2:18])=[CH:16][C:15]([C:19]4[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=4)=[CH:14][N:13]=3)=[CH:8][C:7]=2[O:27][CH3:28])[CH2:3][CH2:2]1.C(N(CC)CC)C.[C:44]([N:49]=[C:50]=S)(=[O:48])[O:45][CH2:46][CH3:47].C1(S(Cl)(=O)=O)C=CC=CC=1>O1CCCC1>[CH:1]1([CH:4]([C:29]2[CH:30]=[N:31][C:32]([O:35][CH3:36])=[CH:33][CH:34]=2)[O:5][C:6]2[CH:26]=[CH:25][C:9]([CH2:10][N:11]3[C:12]4=[N:13][CH:14]=[C:15]([C:19]5[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=5)[CH:16]=[C:17]4[N:18]=[C:50]3[NH:49][C:44](=[O:48])[O:45][CH2:46][CH3:47])=[CH:8][C:7]=2[O:27][CH3:28])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 7369Benzenesulfonyl chlorideHCID 8471Triethylamine2×HCID 85320Ethyl isothiocyanatoformateHCID 118141866N2-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-5-(1-methyl-1H-pyrazol-4-yl)pyridine-2,3-diamine

Product 1

HCID 131733020ethyl (3-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamateYield 68.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N2-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-5-(1-methyl-1H-pyrazol-4-yl)pyridine-2,3-diamine (0.55 g, 1.13 mmol) in tetrahydrofuran (5 mL) was added triethylamine (0.799 g, 7.90 mmol). The resulting mixture was allowed to stir at room temperature. After 15 min, the mixture was treated with ethyl carbonisothiocyanatidate (0.444 g, 3.39 mmol), and the resulting mixture was allowed to stir at room temperature. After 30 min, the mixture was filtered, and the filtrate was concentrated. The residue was dissolved in tetrahydrofuran (5 mL) and was treated with triethylamine (0.799 g, 7.90 mmol) and benzenesulfonyl chloride (0.259 g, 1.43 mmol). The resulting mixture was allowed to stir at room temperature. After 16 h, the mixture was concentrated. Chromatographic purification of the residue (neutral alumina, 50% ethyl acetate in petroleum ether elute) afforded 0.45 g (68%) of ethyl (3-(4-(cyclopropyl(6-methoxypyridin-3-yl)methoxy)-3-methoxybenzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamate as a brown oil.

Workup

  1. stirringto stir at room temperature
  2. waitAfter 30 min
  3. filtrationthe mixture was filtered
  4. concentrationthe filtrate was concentrated
  5. dissolutionThe residue was dissolved in tetrahydrofuran (5 mL)
  6. stirringto stir at room temperature
  7. waitAfter 16 h
  8. concentrationthe mixture was concentrated
  9. customChromatographic purification of the residue (neutral alumina, 50% ethyl acetate in petroleum ether elute)

Sources & evidence

ORD record
ord-74d382eda75e4ad8bd0f3db99c26c05f
Source dataset
uspto-grants-2015_06
Patent number
US09067914B1

Reaction notes

Loading…