Diisopropylethylamine → (S)-3-(5-chloroindole-2-carbonylamino)-2,3-dihydro-1,5-benzoxazepin-4(5H)-one

HRID 31134Notes

Reaction equation

HRID 31134 reaction equation
Cl.[NH2:2][C@@H:3]1[C:9](=[O:10])[NH:8][C:7]2[CH:11]=[CH:12][CH:13]=[CH:14][C:6]=2[O:5][CH2:4]1.[Cl:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20]([C:25](O)=[O:26])=[CH:19]2.ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>O1CCCC1>[Cl:15][C:16]1[CH:17]=[C:18]2[C:22](=[CH:23][CH:24]=1)[NH:21][C:20]([C:25]([NH:2][C@@H:3]1[C:9](=[O:10])[NH:8][C:7]3[CH:11]=[CH:12][CH:13]=[CH:14][C:6]=3[O:5][CH2:4]1)=[O:26])=[CH:19]2

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18599716(S)-7-Amino-6,7-dihydro-9H-5-oxa-9-aza-benzocyclohepten-8-one hydrochloride

Product 1

HCID 11688973(S)-3-(5-chloroindole-2-carbonylamino)-2,3-dihydro-1,5-benzoxazepin-4(5H)-oneYield 88.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Alternatively, to a mixture of (S)-3-amino-2,3-dihydro-1,5-benzoxazepin-4(5H)-one hydrochloride salt (54 mg) (prepared in Itoh, et al., Chem. Pharm. Bull. 1986, 34, 1128-1147), tetrahydrofuran (10 mL), 5-chloroindole-2-carboxylic acid (39 mg), 1-hydroxy-7-azabenzotriazole (31 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (57 mg) stirring at room temperature under argon was added diisopropylethylamine (65 mg). The resulting yellow suspension was stirred for 30 min, during which a solution formed. After evaporation under vacuum, the residue was redissolved in ethyl acetate (50 mL) and the resulting solution was washed sequentially with 1.0 M aqueous hydrochloric acid (25 mL), 1.0 M aqueous sodium hydroxide (25 mL), water (25 mL) and brine (25 mL), dried over anhydrous sodium sulfate, and evaporated under vacuum. The resulting solid crude product was triturated with diethyl ether (20 mL three times), followed by drying under vacuum to provide the title compound (63 mg).

Workup

  1. stirringThe resulting yellow suspension was stirred for 30 min, during which a solution
  2. customformed
  3. customAfter evaporation under vacuum
  4. dissolutionthe residue was redissolved in ethyl acetate (50 mL)
  5. washthe resulting solution was washed sequentially with 1.0 M aqueous hydrochloric acid (25 mL), 1.0 M aqueous sodium hydroxide (25 mL), water (25 mL) and brine (25 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated under vacuum
  8. customThe resulting solid crude product was triturated with diethyl ether (20 mL three times)
  9. customby drying under vacuum

Sources & evidence

ORD record
ord-64212133acf94632a7e80609a2e07332
Source dataset
uspto-grants-2008_09
Patent number
US07425550B2

Reaction notes

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