N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → 4-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide

HRID 1473700Notes

Reaction equation

HRID 1473700 reaction equation
[CH3:1][O:2][C:3]1[CH:15]=[CH:14][C:6]([CH2:7][NH:8][C:9]2[S:10][CH:11]=[CH:12][N:13]=2)=[CH:5][CH:4]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[Cl:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:37](Cl)(=[O:39])=[O:38])=[CH:34][CH:35]=2)[C:30](=[O:41])[N:29]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[CH:28]=1>C1COCC1>[Cl:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([S:37]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:15][CH:14]=3)[C:9]3[S:10][CH:11]=[CH:12][N:13]=3)(=[O:39])=[O:38])=[CH:34][CH:35]=2)[C:30](=[O:41])[N:29]([CH2:42][C:43]2[CH:48]=[CH:47][C:46]([O:49][CH3:50])=[CH:45][CH:44]=2)[CH:28]=1

Participants

5

Reactant 3

HCID 578640N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amineHCID 2733832Lithium HexamethyldisilazideHCID 866877844-Chloro-2-(4-methoxybenzyl)-1-oxo-1,2-dihydroisoquinoline-7-sulfonyl chloride

Product 1

HCID 866877854-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamideYield 48.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A round-bottom flask was charged with N-(4-methoxybenzyl)thiazol-2-amine (0.213 g, 0.967 mmol) and THF (4.40 mL), and the vessel was cooled to −78° C. for 15 minutes. LHMDS (1.0 M in THF) (1.055 mL, 1.055 mmol) was then added drop wise over 1 minute. The reaction was stirred for 10 minutes, and then a solution of 4-chloro-2-(4-methoxybenzyl)-1-oxo-1,2-dihydroisoquinoline-7-sulfonyl chloride (0.350 g, 0.879 mmol) in THF (1.60 mL) was added drop wise. The bath was removed, and the resulting mixture was stirred for 45 minutes, until complete conversion to 4-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide. The reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL), and was washed with ethyl acetate (20 mL×3). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting material was purified via silica gel chromatography (ISCO, 40 g), eluting with 0 to 100% ethyl acetate in heptanes to provide 0.250 g of 4-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide. m/z (ESI) 583.2 (M+H)+.

Workup

  1. customThe bath was removed
  2. stirringthe resulting mixture was stirred for 45 minutes, until complete conversion to 4-chloro-N,2-bis(4-methoxybenzyl)-1-oxo-N-(thiazol-2-yl)-1,2-dihydroisoquinoline-7-sulfonamide
  3. additionThe reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL)
  4. washwas washed with ethyl acetate (20 mL×3)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting material was purified via silica gel chromatography (ISCO, 40 g)
  9. washeluting with 0 to 100% ethyl acetate in heptanes

Sources & evidence

ORD record
ord-657a6808c9a84aea804fe04a05c65847
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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