1,2-Dichloroethane → ((3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl)(4-(1-cyclohexyl-2-(diethylamino)ethyl)piperazin-1-yl)methanone

HRID 1373658Notes

Reaction equation

HRID 1373658 reaction equation
[C:1]([N:5]1[CH2:9][C@@H:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[C@H:7]([C:18](O)=[O:19])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2].C[N:22]1[CH2:27][CH2:26]O[CH2:24][CH2:23]1.[CH:28]1[CH:29]=[CH:30][C:31]2N(O)N=N[C:32]=2[CH:33]=1.[CH2:38](Cl)[CH2:39]Cl.[NH:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1.Cl>ClCCl>[C:1]([N:5]1[CH2:9][C@@H:8]([C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=2[F:17])[C@H:7]([C:18]([N:42]2[CH2:47][CH2:46][N:45]([CH:24]([CH:32]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:33]3)[CH2:23][N:22]([CH2:38][CH3:39])[CH2:27][CH3:26])[CH2:44][CH2:43]2)=[O:19])[CH2:6]1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 4837PiperazineHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 9860579(3S,4R)-1-tert-Butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid

Product 1

HCID 10098568((3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl)(4-(1-cyclohexyl-2-(diethylamino)ethyl)piperazin-1-yl)methanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine 3-carboxylic acid A-2 (40 mg, 0.138 mmol) in dichloromethane (10 mL) was added 4-methylmorpholine (0.023 mL, 0.208 mmol), HOBt (20.6 mg, 0.152 mmol), EDC (39.8 mg, 0.208 mmol), and piperazine K-2 (41.9 mg, 0.138 mmol). The reaction mixture was stirred at room temperature for 18 hrs. The reaction mixture was concentrated, purified by preparative TLC (10:1, CHCl3: 2N NH3 in MeOH) to give a yellow oil, to which was added HCl (1M in ether) and the resulting mixture was concentrated to give the title compound. ESI-MS calc. for C31H50F2N40: 532. Found: 533 (M+H). H1 NMR (500 MHz, CD3OD) δ 7.54–7.40 (m, 1H), 7.00–6.82 (m, 2H), 3.92–3.82 (m, 1H), 3.70–3.40 (m, 3H), 3.40–3.25 (m, 2H), 3.24–3.18 (m, 2H), 3.00–2.80 (m, 2H), 2.78–2.42 (m, 8H), 2.40–2.10 (m, 4H), 1.82–1.60 (m, 6H), 1.41–1.00 (m, 19H),

Workup

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by preparative TLC (10:1, CHCl3: 2N NH3 in MeOH)
  3. customto give a yellow oil
  4. concentrationthe resulting mixture was concentrated

Sources & evidence

ORD record
ord-f0e45fbd752e447daf8c7f26285ba4ae
Source dataset
uspto-grants-2007_01
Patent number
US07160886B2

Reaction notes

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