4-Methylmorpholine → 1-[trans-4-(n-Tert-butoxycarbonylaminomethyl)-n-tert-butoxycarbonyl-l-prolyl]-4-(3-chloro-2-methylphenyl)piperazine

HRID 2185469Notes

Reaction equation

HRID 2185469 reaction equation
CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.[C:20]([O:24][C:25]([NH:27][CH2:28][C@H:29]1[CH2:33][N:32]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[C@H:31]([C:41]([OH:43])=O)[CH2:30]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].Cl.[Cl:45][C:46]1[C:47]([CH3:58])=[C:48]([N:52]2[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]2)[CH:49]=[CH:50][CH:51]=1.ON1C2C=CC=CC=2N=N1>O1CCCC1.CN(C)C=O>[C:37]([O:36][C:34]([NH:32][CH2:33][C@H:29]1[CH2:28][N:27]([C:25]([O:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:26])[C@H:31]([C:41]([N:55]2[CH2:54][CH2:53][N:52]([C:48]3[CH:49]=[CH:50][CH:51]=[C:46]([Cl:45])[C:47]=3[CH3:58])[CH2:57][CH2:56]2)=[O:43])[CH2:30]1)=[O:35])([CH3:40])([CH3:39])[CH3:38]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 213415491-(1,1-Dimethylethyl) (2S,4S)-4-((((1,1-dimethylethoxy)carbonyl)amino)methyl)-1,2-pyrrolidinedicarboxylateHCID 224584741-(3-Chloro-2-methylphenyl)piperazine hydrochloride

Product 1

HCID 540742211-[trans-4-(n-Tert-butoxycarbonylaminomethyl)-n-tert-butoxycarbonyl-l-prolyl]-4-(3-chloro-2-methylphenyl)piperazine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-Methylmorpholine (60 μL) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (94 mg) were added to a solution of trans-4-(N-tert-butoxycarbonylaminomethyl)-N-tert-butoxycarbonyl-L-proline (Compound 109 (D), 120 mg), 1-(3-chloro-2-methylphenyl)piperazine hydrochloride (A, 128 mg) and 1-hydroxybenzotriazole (70 mg) in tetrahydrofuran (6 mL) and N,N-dimethylformamide (2 mL) at room temperature. After stirring at room temperature for 16 hr, the reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid. The organic layer was washed with saturated sodium hydrogen carbonate and brine. After drying over anhydrous sodium sulfate, the organic layer was concentrated in vacuo. The residue was washed with hexane to give the titled compound (98 mg) as a white powder: 1H NMR (400 MHz, ) δ 1.42-1.59 (18H), 1.80-2.00 (br s, 2H), 2.36 (s, 3H), 2.86 (br s, 4H), 2.98 (br s, 0.5H), 3.23 (br s, 2.5H), 3.60-3.80 (6 H), 4.68 (m, 1H), 6.89 (br m, 1H), and 7.11 (m, 2H); mass spectrum (EI+) m/e 511 (M).

Workup

  1. customthe reaction mixture was partitioned between ethyl acetate and 1 N hydrochloric acid
  2. washThe organic layer was washed with saturated sodium hydrogen carbonate and brine
  3. dry with materialAfter drying over anhydrous sodium sulfate
  4. concentrationthe organic layer was concentrated in vacuo
  5. washThe residue was washed with hexane

Sources & evidence

ORD record
ord-11b4075cfb094ce3a614f027563a77ea
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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