Thionyl Chloride → 2-(S)-(4-Chloromethyl-1H-indazol-5-ylmethyl)-succinic acid dimethyl ester hydrochoride

HRID 132154Notes

Reaction equation

HRID 132154 reaction equation
S(Cl)([Cl:3])=O.[CH3:5][O:6][C:7](=[O:26])[C@@H:8]([CH2:14][C:15]1[C:16]([CH2:24]O)=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][N:19]=[CH:18]2)[CH2:9][C:10]([O:12][CH3:13])=[O:11]>ClCCl>[ClH:3].[CH3:5][O:6][C:7](=[O:26])[C@@H:8]([CH2:14][C:15]1[C:16]([CH2:24][Cl:3])=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][N:19]=[CH:18]2)[CH2:9][C:10]([O:12][CH3:13])=[O:11]

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 597318712-(S)-(4-Hydroxymethyl-1H-indazol-5-ylmethyl)-succinic acid dimethyl ester

Product 1

HCID 673178982-(S)-(4-Chloromethyl-1H-indazol-5-ylmethyl)-succinic acid dimethyl ester hydrochorideYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Thionyl chloride (5.0 mL) was added to a solution of 2-(S)-(4-hydroxymethyl-1H-indazol-5-ylmethyl)-succinic acid dimethyl ester (1.53 g, 5.0 mmol) in dichloromethane (30 mL). Reaction mixture was stirred at ambient temperature for 2 hours. Mixture was concentrated in vacuo. Residue was triturated in toluene (30 mL), then concentrated in vacuo. Residue was treated with dichloromethane (30 mL) then concentrated in vacuo. Desired product was obtained in 96% yield as an orange solid. 1H NMR (300 MHz, CDCl3): δ=8.22 (s, 1H), 7.49 (d, J=8.8, 1H), 7.15 (d, J=8.8, 1H), 5.12 (s, 2H), 3.56 (s, 3H), 3.52 (s, 3H), 3.05 (m, 3H), 2.69 (dd, J1=8.1, J2=16.5), 2.54 (m, 1H). MS m/e (M+H)+=325.2.

Workup

  1. customReaction mixture
  2. concentrationMixture was concentrated in vacuo
  3. customResidue was triturated in toluene (30 mL)
  4. concentrationconcentrated in vacuo
  5. additionResidue was treated with dichloromethane (30 mL)
  6. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-4805f662201047b593f4b360af128af7
Source dataset
uspto-grants-2008_06
Patent number
US07384930B2

Reaction notes

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