3-Chloropropionyl chloride → 2-(3,4-dichlorophenyl)-4-(3,5-dimethylbenzoyl)-1-[3-[5-(phenylmethyl)-(1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-yl]-1-oxopropyl]piperazine

HRID 362548Notes

Reaction equation

HRID 362548 reaction equation
C(N(C(C)C)CC)(C)C.[CH3:10][C:11]1[CH:12]=[C:13]([CH:30]=[C:31]([CH3:33])[CH:32]=1)[C:14]([N:16]1[CH2:21][CH2:20][NH:19][CH:18]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)[CH2:17]1)=[O:15].Cl[CH2:35][CH2:36][C:37](Cl)=[O:38].Br.Br.[CH2:42]([N:49]1[CH2:54][C@@H:53]2[CH2:55][C@H:50]1[CH2:51][NH:52]2)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>C(Cl)Cl>[Cl:29][C:24]1[CH:23]=[C:22]([CH:18]2[CH2:17][N:16]([C:14](=[O:15])[C:13]3[CH:30]=[C:31]([CH3:33])[CH:32]=[C:11]([CH3:10])[CH:12]=3)[CH2:21][CH2:20][N:19]2[C:37](=[O:38])[CH2:36][CH2:35][N:52]2[CH2:51][C@@H:50]3[CH2:55][C@H:53]2[CH2:54][N:49]3[CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH:27]=[CH:26][C:25]=1[Cl:28]

Participants

6

Reactant 4

HCID 693643-Chloropropionyl chlorideHCID 81531Diisopropylethylamine2×HCID 10292159(+)-(3,5-Dimethylbenzoyl)-3-(3,4-dichlorophenyl)piperazineHCID 14612542(1S,4S)-2-Benzyl-2,5-diazabicyclo(2.2.1)heptane--hydrogen bromide (1/2)

Product 1

HCID 229422702-(3,4-dichlorophenyl)-4-(3,5-dimethylbenzoyl)-1-[3-[5-(phenylmethyl)-(1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-yl]-1-oxopropyl]piperazineYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cooled solution of CH2Cl2 (10 mL) containing diisopropylethylamine (0.275 mL, 2.0 mmol) and [3,5-dimethylbenzoyl]-3-(3,4-dichlorophenyl)piperazine (Enantiomer B) (Example 4) (305 mg, 0.84 mmol) was added chloropropionyl chloride (0.075 mL, 0.8 mmol). The reaction mixture was allowed to warm to room temperature. After 20 minutes, (1S,4S)-2-benzyl-2,5-diazabicyclo(2.2.1)heptane 2HBr (297 mg, 0.85 mmol) and diisopropylethylamine (0.275 mL, 2.0 mmol) were added and the mixture was left over night, after which the reaction mixture was concentrated. The product was purified by flash chromatography on flash grade silica gel, eluting with 30:1:0.1 CH2Cl2 /MeOH/NH3 to give a foamy solid (140 mg, 0.23 mmol, 29%), High Res. MS:[M+1]+ calcd. for C34H39Cl2N4O2 605.2450; Found, 605.2465.

Workup

  1. waitthe mixture was left over night
  2. concentrationafter which the reaction mixture was concentrated
  3. customThe product was purified by flash chromatography on flash grade silica gel
  4. washeluting with 30:1:0.1 CH2Cl2 /MeOH/NH3

Sources & evidence

ORD record
ord-3a37d649fd084f85b99ca1d5cc2f3a0f
Source dataset
uspto-grants-1999_02
Patent number
US05869488

Reaction notes

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