Succinic Acid → 7-Chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine Succinate

HRID 1670566Notes

Reaction equation

HRID 1670566 reaction equation
[Cl:1][C:2]1[CH:12]=[CH:11][C:5]2[CH2:6][CH2:7][NH:8][CH2:9][CH2:10][C:4]=2[C:3]=1[CH2:13][S:14][C:15]1[S:16][C:17]([NH:20][CH2:21][CH:22]2[CH2:24][CH2:23]2)=[N:18][N:19]=1.[C:25]([OH:32])(=[O:31])[CH2:26][CH2:27][C:28]([OH:30])=[O:29]>C(O)C>[C:25]([OH:32])(=[O:31])[CH2:26][CH2:27][C:28]([OH:30])=[O:29].[Cl:1][C:2]1[CH:12]=[CH:11][C:5]2[CH2:6][CH2:7][NH:8][CH2:9][CH2:10][C:4]=2[C:3]=1[CH2:13][S:14][C:15]1[S:16][C:17]([NH:20][CH2:21][CH:22]2[CH2:24][CH2:23]2)=[N:18][N:19]=1

Participants

4

Reactant 2

HCID 1110Succinic AcidHCID 598223037-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 673355277-Chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine SuccinateYield 100.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 3-tert-butoxycarbonyl-7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.082 g, 0.171 mmol) in anhydrous DCM (3.5 mL) at room temperature add trifluoroacetic acid (3.5 mL) and stir the solution at room temperature overnight. Concentrate in. vacuo and elute the residue through a SCX column (20 g). Dissolve the residue in DCM, load the solution on to a RediSep® column (12 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 90:10 DCM/2M ammonia in methanol over 33 min; 35 mL/min) to afford 7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.051 g, 78%). MS (ES+) m/z: 381.1 (M+H)+. To a solution of 7-chloro-6-[5-(cyclopropylmethyl-amino)-[1,3,4]thiadiazol-2-ylthiomethyl]-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.044 g, 0.116 mmol) in absolute ethanol (5 mL), add succinic acid (0.014 g, 0.116 mmol). After acid dissolves, concentrate the reaction mixture in vacuo. Combine the residue with MTBE, concentrate in vacuo several times and dry under high vacuum at room temperature overnight to obtain the title compound (0.058 g, 100%) as a white foam. MS (ES+) m/z: 381.0 (M+H)+.

Workup

  1. dissolutionAfter acid dissolves
  2. concentrationconcentrate the reaction mixture in vacuo
  3. concentrationconcentrate in vacuo several times
  4. customdry under high vacuum at room temperature overnight

Sources & evidence

ORD record
ord-e71b2433897f413eaec0e2cc86e8e8e2
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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