Methanesulfonyl chloride → HCID 52938544, compound

HRID 1053742Notes

Reaction equation

HRID 1053742 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:12][CH2:11][CH2:10][C:9]2[C:8]([C:13]3[N:17]=[C:16]([C:18]4[CH:19]=[CH:20][C:21]([O:26][CH:27]([CH3:29])[CH3:28])=[C:22]([CH:25]=4)[C:23]#[N:24])[O:15][N:14]=3)=[CH:7][CH:6]=[CH:5][C:4]1=2.[CH3:30][S:31](Cl)(=[O:33])=[O:32]>C(Cl)Cl>[C:23]([C:22]1[CH:25]=[C:18]([C:16]2[O:15][N:14]=[C:13]([C:8]3[CH:7]=[CH:6][CH:5]=[C:4]4[C:9]=3[CH2:10][CH2:11][CH2:12][C@H:3]4[NH:2][S:31]([CH3:30])(=[O:33])=[O:32])[N:17]=2)[CH:19]=[CH:20][C:21]=1[O:26][CH:27]([CH3:29])[CH3:28])#[N:24]

Participants

4

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 67198744HCID 67198744, compound

Product 1

HCID 52938544HCID 52938544, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedure 6: To a stirring solution of (R)-5-(3-(5-amino-5,6,7,8-tetrahydronaphthalen-1-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile hydrochloride 3 (20 mg, 0.05 mmol) in DCM (1 mL) at 0° C. was added TEA (20 μL, 0.15 mmol) and methanesulfonyl chloride (4.5 μL, 0.06 mmol). The mixture was allowed to warm to room temperature over 2 h. The solvent was evaporated and crude mixture was purified by preparative HPLC to afford 12.8 mg (58%) of (R)-N-(5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)methanesulfonamide 28. LCMS-ESI (m/z) calculated for C23H24N4O4S: 452.5; found 453.1 [M+H]+, tR=3.68 min. 1H NMR (400 MHz, CDCl3) δ 8.40 (t, J=3.5 Hz, 1H), 8.32 (dd, J=8.9, 2.2 Hz, 1H), 7.96 (dd, J=7.7, 1.1 Hz, 1H), 7.67 (d, J=7.7 Hz, 1H), 7.38 (t, J=7.7 Hz, 1H), 7.16-7.07 (m, 1H), 4.88-4.70 (m, 1H), 4.54 (d, J=8.4 Hz, 1H), 3.19 (dt, J=18.0, 5.9 Hz, 1H), 3.10 (d, J=5.0 Hz, 3H), 3.09-2.95 (m, 1H), 2.14 (qt, J=14.5, 7.3 Hz, 1H), 2.06-1.83 (m, 3H), 1.47 (t, J=5.5 Hz, 6H).

Workup

  1. customPrepared
  2. customThe solvent was evaporated
  3. customcrude mixture was purified by preparative HPLC

Sources & evidence

ORD record
ord-4688ae29aec746bf92218794d314893e
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

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