Methyl (chlorosulfonyl)acetate → HCID 67200787, compound

HRID 1053743Notes

Reaction equation

HRID 1053743 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][O:31][C:32](=[O:38])[CH2:33][S:34](Cl)(=[O:36])=[O:35]>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:34]([CH2:33][C:32]([O:31][CH3:30])=[O:38])(=[O:36])=[O:35])[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 11435213Methyl (chlorosulfonyl)acetate2×HCID 67198744HCID 67198744, compound

Product 1

HCID 67200787HCID 67200787, compoundYield 58.2%

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 (0.15 g, 0.37 mmol) in DCM (5 mL) were added TEA (76 μL, 0.55 mmol) and methyl-2-(chlorosulfonyl)acetate (76 mg, 0.44 mmol). Additional TEA and methyl-2-(chlorosulfonyl)acetate were added to drive the reaction to completion over 24 h. The crude reaction mixture was partitioned between DCM and saturated NaHCO3. The organic layer was dried over Na2SO4, concentrated, and purified by column chromatography (EA/hexanes) to give 0.11 g (57%) of (R)-methyl 2-(N-(5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydronaphthalen-1-yl)sulfamoyl)acetate INT-14. LCMS-ESI (m/z) calculated for C25H26N4O6S: 510.6; found 511.1 [M+H]+, tR=3.73 min. 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J=2.2 Hz, 1H), 8.33 (dd, J=8.9, 2.2 Hz, 1H), 8.01-7.93 (m, 1H), 7.74 (d, J=7.8 Hz, 1H), 7.39 (t, J=7.8 Hz, 1H), 7.12 (d, J=9.0 Hz, 1H), 5.00 (d, J=8.4 Hz, 1H), 4.81 (dq, J=18.3, 5.9 Hz, 2H), 4.25-4.00 (m, 2H), 3.83 (s, 3H), 3.20 (dt, J=18.1, 5.9 Hz, 1H), 3.12-2.97 (m, 1H), 2.22-2.01 (m, 2H), 2.02-1.83 (m, 2H), 1.48 (d, J=6.1 Hz, 6H).

Workup

  1. customPrepared
  2. customthe reaction to completion over 24 h
  3. customThe crude reaction mixture
  4. customwas partitioned between DCM and saturated NaHCO3
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. custompurified by column chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-2e8fff97036a4458ab7d08c546ddc997
Source dataset
uspto-grants-2016_07
Patent number
US09394264B2

Reaction notes

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