Benzyl Alcohol → Benzyl {[3-(7-fluoro-1-hydroxy-3-oxo-4,4-dipropyl-3,4-dihydronaphthalen-2-yl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]amino}sulfonylcarbamate

HRID 494483Notes

Reaction equation

HRID 494483 reaction equation
Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[CH2:8]([OH:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[NH2:16][C:17]1[CH:47]=[CH:46][C:20]2[NH:21][C:22]([C:27]3[C:28](=[O:45])[C:29]([CH2:42][CH2:43][CH3:44])([CH2:39][CH2:40][CH3:41])[C:30]4[C:35]([C:36]=3[OH:37])=[CH:34][C:33]([F:38])=[CH:32][CH:31]=4)=[N:23][S:24](=[O:26])(=[O:25])[C:19]=2[CH:18]=1.C(N(CC)CC)C>ClCCl>[F:38][C:33]1[CH:34]=[C:35]2[C:30]([C:29]([CH2:39][CH2:40][CH3:41])([CH2:42][CH2:43][CH3:44])[C:28](=[O:45])[C:27]([C:22]3[NH:21][C:20]4[CH:46]=[CH:47][C:17]([NH:16][S:2]([NH:5][C:6](=[O:7])[O:15][CH2:8][C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=5)(=[O:4])=[O:3])=[CH:18][C:19]=4[S:24](=[O:25])(=[O:26])[N:23]=3)=[C:36]2[OH:37])=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 1363756033-(7-amino-1,1-dioxido-4H-1,2,4-benzothiadiazin-3-yl)-6-fluoro-4-hydroxy-1,1-dipropylnaphthalen-2(1H)-one

Product 1

HCID 136375602Benzyl {[3-(7-fluoro-1-hydroxy-3-oxo-4,4-dipropyl-3,4-dihydronaphthalen-2-yl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]amino}sulfonylcarbamateYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of chlorosulfonyl isocyanate (14.2 μL, 0.163 mmol) in dichloromethane (2 mL) was treated with benzyl alcohol (17 μL, 0.163 mmol) followed by stirring at ambient temperature for 30 min. The solution was added to the product of Example 17C (62 mg, 0.136 mmol) in dichloromethane (2 mL) followed by addition of triethylamine (76 μL, 0.54 mmol). The solution was stirred at ambient temperature for 2 h, and diluted with dichloromethane and extracted with water (2×). Drying (Na2SO4) and concentration in vacuo afforded the title compound (28 mg, 31%) as a brown solid. 1H NMR (300 MHz, DMSO-d6): δ 0.69 (m, 8 H) 0.92 (m, 2 H) 2.00 (dd, J=12.13, 8.82 Hz, 2 H) 2.16 (m, 2 H) 5.12 (s, 2 H) 7.35 (m, 5 H) 7.47 (dd, J=8.82, 2.57 Hz, 1 H) 7.63 (m, 3 H) 7.82 (m, 2 H) 11.09 (s, 1 H) 12.13 (s, 1 H) 13.54 (s, 1 H).

Workup

  1. stirringThe solution was stirred at ambient temperature for 2 h
  2. extractionextracted with water (2×)
  3. customDrying
  4. concentration(Na2SO4) and concentration in vacuo

Sources & evidence

ORD record
ord-b33c6903ec2147a9bfcc454f64afba93
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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