4-Toluenesulfonyl chloride → HCID 86621626, compound

HRID 2246967Notes

Reaction equation

HRID 2246967 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C@@H:14]([O:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]4[O:25][CH2:24][CH2:23][N:22]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[C:21]=4[CH:31]=3)[CH2:13][N:12]([S:32]([C:35]3[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=3)(=[O:34])=[O:33])[C@H:11]([CH2:42][C@@H:43]([NH2:45])[CH3:44])[CH2:10]2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[N:53]#[C:54]Br.[C:56]1([CH3:66])[CH:61]=[CH:60][C:59]([S:62](Cl)(=[O:64])=[O:63])=[CH:58][CH:57]=1>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@@H:9]2[C@@H:14]([O:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]4[O:25][CH2:24][CH2:23][N:22]([CH2:26][CH2:27][CH2:28][O:29][CH3:30])[C:21]=4[CH:31]=3)[CH2:13][N:12]([S:32]([C:35]3[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=3)(=[O:33])=[O:34])[C@H:11]([CH2:42][C@@H:43]([N:45]([C:54]#[N:53])[S:62]([C:59]3[CH:60]=[CH:61][C:56]([CH3:66])=[CH:57][CH:58]=3)(=[O:64])=[O:63])[CH3:44])[CH2:10]2)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471Triethylamine2×HCID 10476Cyanogen BromideHCID 68443034HCID 68443034, compound

Product 1

HCID 86621626HCID 86621626, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of 399 mg of (S)-2-[(2S,4R,5R)-4-(4-methoxy-phenyl)-5-[4-(3-methoxy-propyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-1-(toluene-4-sulfonyl)-piperidin-2-yl]-1-methyl-ethylamine in 5 ml of dichloromethane are added 0.12 ml triethylamine and 66 mg of cyanogenbromide at room temperature. The reaction mixture is stirred for 2 hours, followed by the addition of 0.32 ml of triethylamine, 178 mg of 4-toluenesulfonyl chloride and 7 mg of 4-N-dimethylaminopyridine. The reaction mixture is heated to 50° C. for 4 hours and subsequently washed with 1N hydrochloric acid solution and extracted with dichloromethane. The organic phases are combined, dried and concentrated under reduced pressure. The residue is purified by flash chromatography (SiO2 60 F) to afford the title compound as a yellow oil. Rf=0.16 (EtOAc-heptane 1:1); Rt=−5.71.

Workup

  1. washsubsequently washed with 1N hydrochloric acid solution
  2. extractionextracted with dichloromethane
  3. customdried
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by flash chromatography (SiO2 60 F)

Sources & evidence

ORD record
ord-1c6eed0ec0654adeb37a8db80742db67
Source dataset
uspto-grants-2010_03
Patent number
US07687495B2

Reaction notes

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