Triethylamine → 3-Chloro-n-({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)propane-1-sulfonamide

HRID 494676Notes

Reaction equation

HRID 494676 reaction equation
[NH2:1][CH2:2][C:3]1[C:11]2[S:10](=[O:13])(=[O:12])[N:9]=[C:8]([C:14]3[C:15](=[O:32])[C@@:16]([CH2:26][CH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:25])[C:17]4[C:22]([C:23]=3[OH:24])=[CH:21][CH:20]=[CH:19][CH:18]=4)[NH:7][C:6]=2[S:5][CH:4]=1.C(N(CC)CC)C.[Cl:40][CH2:41][CH2:42][CH2:43][S:44](Cl)(=[O:46])=[O:45]>CN(C)C=O.O>[Cl:40][CH2:41][CH2:42][CH2:43][S:44]([NH:1][CH2:2][C:3]1[C:11]2[S:10](=[O:13])(=[O:12])[N:9]=[C:8]([C:14]3[C:15](=[O:32])[C@@:16]([CH2:26][CH2:27][C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:25])[C:17]4[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:23]=3[OH:24])[NH:7][C:6]=2[S:5][CH:4]=1)(=[O:46])=[O:45]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 154103-Chloropropanesulphonyl chlorideHCID 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 1359532923-Chloro-n-({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)propane-1-sulfonamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of Example 186B (64 mg, 0.14 mmol) in 1.5 mL of N,N-dimethyl formamide was cooled to 0° C., treated with triethylamine (30 μL, 0.28 mmol) and 3-chloropropylsulfonyl chloride (19 μL, 0.15 mmol), stirred for 30 minutes, allowed to warm to room temp, stirred for 2 h, diluted with water and extracted with ethyl acetate. The organic phase was washed with water and concentrated in vacuo to afford a solid. This crude material was purified by chromatography on silica gel with a gradient of methanol in dichloromethane (0-2%) to afford the title compound as a pale compound (42 mg, 64%). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.39 (td, J=12.8, 3.5 Hz, 1H), 0.72 (s, 9H), 0.82 (m, 1H), 1.56 (s, 3H), 2.13 (m, 4H), 3.21 (m, 2H), 3.75 (t, J=6.4 Hz, 2H), 4.28 (d, J=5.9 Hz, 2H), 7.33 (s, 1H), 7.51 (m, 1H), 7.72 (m, 2H), 7.90 (t, J=6.3 Hz, 1H), 8.13 (d, J=7.7 Hz, 1H), 14.09 (s, 1H); MS (APCI−) m/z 612 (M−H)−; Anal calc'd for C26H32ClN3O6S3: C, 50.84; H, 5.25; N, 6.84. found: C, 51.07; H, 5.28; N, 6.51.

Workup

  1. stirringstirred for 2 h
  2. extractionextracted with ethyl acetate
  3. washThe organic phase was washed with water
  4. concentrationconcentrated in vacuo
  5. customto afford a solid
  6. customThis crude material was purified by chromatography on silica gel with a gradient of methanol in dichloromethane (0-2%)

Sources & evidence

ORD record
ord-2997bc0afd8741249f7547dfc66fd800
Source dataset
uspto-grants-2009_05
Patent number
US07538105B2

Reaction notes

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