Diisopropylethylamine → Tert-butyl [({3-[4-(2-cyclopropylethyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-1,2,4-benzothiadiazin-7-yl}amino)sulfonyl]acetate

HRID 494639Notes

Reaction equation

HRID 494639 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:29])[C:14]([CH2:24][CH2:25][CH:26]4[CH2:28][CH2:27]4)([CH3:23])[C:15]4[C:20]([C:21]=3[OH:22])=[CH:19][CH:18]=[CH:17][CH:16]=4)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.C(N(CC)C(C)C)(C)C.[C:41]([O:45][C:46](=[O:52])[CH2:47][S:48](Cl)(=[O:50])=[O:49])([CH3:44])([CH3:43])[CH3:42]>ClCCl>[C:41]([O:45][C:46](=[O:52])[CH2:47][S:48]([NH:1][C:2]1[CH:31]=[CH:30][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:29])[C:14]([CH2:24][CH2:25][CH:26]4[CH2:28][CH2:27]4)([CH3:23])[C:15]4[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:21]=3[OH:22])=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1)(=[O:49])=[O:50])([CH3:44])([CH3:42])[CH3:43]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 43350783Tert-butyl 2-(chlorosulfonyl)acetateHCID 1363848543-(7-Amino-1,1-dioxido-4h-1,2,4-benzothiadiazin-3-yl)-1-(2-cyclopropylethyl)-4-hydroxy-1-methylnaphthalen-2(1h)-one

Product 1

HCID 137194539Tert-butyl [({3-[4-(2-cyclopropylethyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-1,2,4-benzothiadiazin-7-yl}amino)sulfonyl]acetateYield 30.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of Example 158 (0.070 g, 0.160 mmol) in dichloromethane containing N,N-diisopropylethylamine (0.036 mL, 0.208 mmol) was added chlorosulfonyl-acetic acid tert-butyl ester (0.041 g, 0.192 mmol). The reaction mixture was stirred overnight and then partitioned between ethyl acetate and water. The organic layer was washed sequentially with 10% 1N HCl in water, bicarb, and brine. The product was purified by flash chromatography on SiO2 eluting with 0-50% ethyl acetate/hexanes yielding the title compound (0.030 g, 30.5% yield) as a light yellow solid. 1H NMR (300 MHz, DMSO-d6): δ ppm−0.23 (dd, J=9.01, 4.23 Hz, 2H) 0.25 (d, J=6.62 Hz, 2H) 0.45 (m, 2H) 0.85 (m, 1H) 1.25 (m, 1H) 1.39 (s, 9H) 1.57 (m, 3H) 2.34 (m, 1H) 4.22 (m, 2H) 7.55 (m, 2H) 7.62 (dd, J=10.29, 2.21 Hz, 2H) 7.75 (m, 3H) 8.15 (d, J=7.72 Hz, 1H) 10.61 (s, 1H) 13.73 (m, 1H). MS (ESI+) m/z=516 (M+H)+.

Workup

  1. custompartitioned between ethyl acetate and water
  2. washThe organic layer was washed sequentially with 10% 1N HCl in water, bicarb, and brine

Sources & evidence

ORD record
ord-e23d2778f4e94e74b54871f3e3125cf6
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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