Acetic Acid → (1R,2S)-5'-(4-chlorophenyl)-2,6',7'-trimethylspiro[cyclopropane-1,3'-thieno[2,3-e][1,4]diazepin]-2'(1'H)-one

HRID 1772359Notes

Reaction equation

HRID 1772359 reaction equation
COC(=O)[NH:4][C@:5]1([C:9](=[O:27])[NH:10][C:11]2[S:12][C:13]([CH3:26])=[C:14]([CH3:25])[C:15]=2[C:16](=O)[C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[CH2:7][C@@H:6]1[CH3:8].N1CCCCC1.C(O)(=O)C>CN(C=O)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([C:16]2[C:15]3[C:14]([CH3:25])=[C:13]([CH3:26])[S:12][C:11]=3[NH:10][C:9](=[O:27])[C@:5]3([CH2:7][C@@H:6]3[CH3:8])[N:4]=2)=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 8082PiperidineHCID 131734667methyl-(1R,2S)-1-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-ylcarbamoyl)-2-methylcyclopropylcarbamate

Product 1

HCID 136338067(1R,2S)-5'-(4-chlorophenyl)-2,6',7'-trimethylspiro[cyclopropane-1,3'-thieno[2,3-e][1,4]diazepin]-2'(1'H)-oneYield 72.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A round bottomed flask was charged with 9H-fluoren-9-yl)methyl-(1R,2S)-1-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-ylcarbamoyl)-2-methylcyclopropylcarbamate (225 mg, 0.385 mmol) and a stir bar. DMF (16 mL, 0.02 M) was added, followed by piperidine (4 mL, 40.4 mmol), and the solution was stirred at room temperature 15 min. The solution was washed with water, extracted twice with ethyl acetate, washed with brine, and concentrated before being taken up in ethanol (25 mL). Acetic acid (12.5 mL, 218 mmol) was added, and the solution was stirred at 90° C. 3 h before being concentrated with celite and purified by column chromatography to give (1R,2S)-5′-(4-chlorophenyl)-2,6′,7′-trimethylspiro[cyclopropane-1,3′-thieno[2,3-e][1,4]diazepin]-2′(1′H)-one (Compound 218) as a light yellow amorphous solid (96 mg). LRMS (M+H)+: 345 m/z.

Workup

  1. washThe solution was washed with water
  2. extractionextracted twice with ethyl acetate
  3. washwashed with brine
  4. concentrationconcentrated
  5. stirringthe solution was stirred at 90° C
  6. concentration3 h before being concentrated with celite
  7. custompurified by column chromatography

Sources & evidence

ORD record
ord-6685c56ab7154272a69a1d233e76ca7d
Source dataset
uspto-grants-2016_02
Patent number
US09249161B2

Reaction notes

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