Diisopropylethylamine → 4-[4-(2-Methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid methyl ester

HRID 736736Notes

Reaction equation

HRID 736736 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH:10]([NH2:11])[CH2:9][CH2:8][O:7][CH2:6]1)=[O:4].Cl.[CH3:13][C:14]1[CH:23]=[C:22]([CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=2)[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:1][O:2][C:3]([CH:5]1[CH:10]([NH:11][S:32]([C:29]2[CH:30]=[CH:31][C:26]([O:25][CH2:24][C:22]3[C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[N:15]=[C:14]([CH3:13])[CH:23]=3)=[CH:27][CH:28]=2)(=[O:33])=[O:34])[CH2:9][CH2:8][O:7][CH2:6]1)=[O:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 20747811methyl 4-aminotetrahydro-2H-pyran-3-carboxylateHCID 866078654-(2-Methylquinolin-4-ylmethoxy)benzenesulfonyl chloride hydrochloride

Product 1

HCID 688172194-[4-(2-Methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid methyl esterYield 82.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a mixture of 0.5 g (2.79 mmol) of 4-amino-tetrahydro-pyran-3-carboxylic acid methyl ester [WO 01/70673, Example 207] and 4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfonyl chloride hydrochloride (1.0 g, 2.94 mmol) in N,N-dimethylformamide (10 mL) was added N,N-diisopropylethylamine (1.02 mL, 5.88 mmol) at 0° C. The solution was allowed to warm to 25° C. over 19 h. The DMF was removed in vacuo and the resulting solid was partitioned between ethyl acetate (100 mL) and water (30 mL). The aqueous layer was washed with ethyl acetate (2×50 mL). ). The organic layer was dried over MgSO4, filtered and concentrated to obtain a crude oil (1.48 g). The crude product was purified by Biotage Flash 40M chromatography, eluting with 1:4 ethyl acetate-hexanes, to afford 4-[4-(2-methyl-quinolin-4-ylmethoxy)-benzenesulfonylamino]-tetrahydro-pyran-3-carboxylic acid methyl ester as a white solid (1.08 g, 78%). MS: 471 (M+H)+

Workup

  1. customThe DMF was removed in vacuo
  2. customthe resulting solid was partitioned between ethyl acetate (100 mL) and water (30 mL)
  3. washThe aqueous layer was washed with ethyl acetate (2×50 mL)
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto obtain a crude oil (1.48 g)
  8. customThe crude product was purified by Biotage Flash 40M chromatography
  9. washeluting with 1:4 ethyl acetate-hexanes

Sources & evidence

ORD record
ord-095880805f6e4f16a26a4d208a4cda9d
Source dataset
uspto-grants-2009_09
Patent number
US07595327B2

Reaction notes

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