Methyl (chlorosulfonyl)acetate → HCID 58344673, compound

HRID 1051085Notes

Reaction equation

HRID 1051085 reaction equation
Cl.[NH2:2][C@@H:3]1[C:11]2[C:6](=[C:7]([C:12]3[N:16]=[C:15]([C:17]4[CH:18]=[CH:19][C:20]([O:25][CH:26]([CH3:28])[CH3:27])=[C:21]([CH:24]=4)[C:22]#[N:23])[O:14][N:13]=3)[CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1.[CH3:29][O:30][C:31](=[O:37])[CH2:32][S:33](Cl)(=[O:35])=[O:34]>C(Cl)Cl>[C:22]([C:21]1[CH:24]=[C:17]([C:15]2[O:14][N:13]=[C:12]([C:7]3[CH:8]=[CH:9][CH:10]=[C:11]4[C:6]=3[CH2:5][CH2:4][C@@H:3]4[NH:2][S:33]([CH2:32][C:31]([O:30][CH3:29])=[O:37])(=[O:35])=[O:34])[N:16]=2)[CH:18]=[CH:19][C:20]=1[O:25][CH:26]([CH3:28])[CH3:27])#[N:23]

Participants

4

Reactant 2

HCID 11435213Methyl (chlorosulfonyl)acetateHCID 67313311HCID 67313311, compound

Product 1

HCID 58344673HCID 58344673, compoundYield 70.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedure 16: To a stirred solution of (S)-5-(3-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 50 (0.36 g, 1.0 mmol) in DCM (5 mL) was added methyl-2-(chlorosulfonyl)acetate (112 mg, 0.6 mmol). After 0.5 h, the crude reaction was partitioned between DCM and saturated NaHCO3. The organic layer was dried over MgSO4, concentrated, and purified by column chromatography (EA/hexanes) to give 0.21 g (42%) of (S)-methyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate 72. LCMS-ESI (m/z) calculated for C24H24N4O6S: 496.1. found 519.1 [M+Na]+, tR=3.71 min. 1H NMR (400 MHz, CDCl3) δ 8.41 (d, J=2.1 Hz, 1H), 8.32 (dd, J=8.9, 2.2 Hz, 1H), 8.13 (d, J=7.7 Hz, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.43 (t, J=7.7 Hz, 1H), 7.11 (d, J=9.0 Hz, 1H), 5.20-5.00 (m, 2H), 4.78 (hept, J=6.2 Hz, 1H), 4.16 (d, J=14.9 Hz, 1H), 4.08 (d, J=14.9 Hz, 1H), 3.82 (s, 3H), 3.51 (ddd, J=17.4, 8.9, 3.5 Hz, 1H), 3.28-3.11 (m, 1H), 2.71 (dtd, J=11.3, 8.1, 3.6 Hz, 1H), 2.16-2.02 (m, 1H), 1.46 (d, J=6.1 Hz, 6H). (R)-methyl 2-(N-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)sulfamoyl)acetate was synthesized in an analogous fashion from (R)-5-(3-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 49.

Workup

  1. customPrepared
  2. customthe crude reaction
  3. customwas partitioned between DCM and saturated NaHCO3
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated
  6. custompurified by column chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-6042bc9d93784e5aa8b6976a309bd15d
Source dataset
uspto-grants-2016_07
Patent number
US09388147B2

Reaction notes

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