Benzyl Alcohol → Benzyl [({3-[(4r)-4-(3,3-dimethylbutyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-7-yl}methyl)amino]sulfonylcarbamate

HRID 2224995Notes

Reaction equation

HRID 2224995 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][CH2:17][C:18]1[C:26]2[S:25](=[O:28])(=[O:27])[N:24]=[C:23]([C:29]3[C:30](=[O:47])[C@@:31]([CH2:41][CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:40])[C:32]4[C:37]([C:38]=3[OH:39])=[CH:36][CH:35]=[CH:34][CH:33]=4)[NH:22][C:21]=2[S:20][CH:19]=1.C(N(CC)CC)C>ClCCl>[CH3:44][C:43]([CH3:46])([CH3:45])[CH2:42][CH2:41][C@:31]1([CH3:40])[C:32]2[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:38]([OH:39])=[C:29]([C:23]2[NH:22][C:21]3[S:20][CH:19]=[C:18]([CH2:17][NH:16][S:2]([NH:5][C:6](=[O:7])[O:15][CH2:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)(=[O:4])=[O:3])[C:26]=3[S:25](=[O:28])(=[O:27])[N:24]=2)[C:30]1=[O:47]

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 70918Chlorosulfonyl isocyanateHCID 135953293(1r)-3-[7-(Aminomethyl)-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-3-yl]-1-(3,3-dimethylbutyl)-4-hydroxy-1-methylnaphthalen-2(1h)-one

Product 1

HCID 137194541Benzyl [({3-[(4r)-4-(3,3-dimethylbutyl)-1-hydroxy-4-methyl-3-oxo-3,4-dihydronaphthalen-2-yl]-1,1-dioxido-4h-thieno[2,3-e][1,2,4]thiadiazin-7-yl}methyl)amino]sulfonylcarbamateYield 70.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of chlorosulfonylisocyanate (9 μL, 0.1 mmol) in 1 mL of dichloromethane was treated with benzyl alcohol (10 μL, 0.9 mmol), stirred for 30 minutes, treated with a solution of Example 186B (36 mg, 0.07 mmol) and triethylamine (40 μL, 0.3 mmol) in 1 mL of dichloromethane, stirred for 1.5 h, diluted with dichloromethane, washed with 1 N aqueous HCl and water, and concentrated in vacuo. The crude material was purified by chromatography on silica gel with a gradient of methanol in dichloromethane (0-3%) to afford the title compound (34 mg, 67%). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.40 (td, J=12.9, 3.7 Hz, 1 H), 0.72 (s, 9 H), 0.81 (td, J=12.8, 4.6 Hz, 1 H), 1.54 (s, 3 H), 2.04 (m, 1 H), 2.20 (m, 1 H), 4.27 (d, J=5.5 Hz, 2 H), 5.17 (s, 2 H), 7.19 (s, 1 H), 7.37 (m, 5 H), 7.49 (m, 1 H), 7.62 (s, 1 H), 7.70 (d, J=3.7 Hz, 2 H), 8.11 (d, J=7.7 Hz, 1 H), 8.55 (t, J=6.3 Hz, 1 H), 11.52 (s, 1 H), 14.44 (s, 1 H); MS (APCI−) m/z 685 (M−H)−, m/z 472 (M-[SO2NHCbz]-H)−.

Workup

  1. stirringstirred for 1.5 h
  2. washwashed with 1 N aqueous HCl and water
  3. concentrationconcentrated in vacuo
  4. customThe crude material was purified by chromatography on silica gel with a gradient of methanol in dichloromethane (0-3%)

Sources & evidence

ORD record
ord-4bc9a2fd551b4ff49b2580337dc20009
Source dataset
uspto-grants-2008_05
Patent number
US07378414B2

Reaction notes

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