4-Methylmorpholine → 1-[trans-4-(n-Tert-butoxycarbonylglycylamino)-n-tert-butoxycarbonyl-l-prolyl]-4-(2-chloro-5-methylphenoxy)piperidine

HRID 2185486Notes

Reaction equation

HRID 2185486 reaction equation
CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.[C:20]([O:24][C:25]([NH:27][CH2:28][C:29]([NH:31][C@H:32]1[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C@H:34]([C:44](O)=[O:45])[CH2:33]1)=[O:30])=[O:26])([CH3:23])([CH3:22])[CH3:21].[Cl:47][C:48]1[CH:60]=[CH:59][C:58]([CH3:61])=[CH:57][C:49]=1[O:50][CH:51]1[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]1.ON1C2C=CC=CC=2N=N1>O1CCCC1.CN(C)C=O>[C:20]([O:24][C:25]([NH:27][CH2:28][C:29]([NH:31][C@H:32]1[CH2:36][N:35]([C:37]([O:39][C:40]([CH3:42])([CH3:43])[CH3:41])=[O:38])[C@H:34]([C:44]([N:54]2[CH2:53][CH2:52][CH:51]([O:50][C:49]3[CH:57]=[C:58]([CH3:61])[CH:59]=[CH:60][C:48]=3[Cl:47])[CH2:56][CH2:55]2)=[O:45])[CH2:33]1)=[O:30])=[O:26])([CH3:22])([CH3:21])[CH3:23]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 171951004-(2-Chloro-5-methylphenoxy)piperidineHCID 21341559trans-4-(N-tert-butoxycarbonylglycyl)amino-N-tert-butoxycarbonyl-L-proline

Product 1

HCID 701767841-[trans-4-(n-Tert-butoxycarbonylglycylamino)-n-tert-butoxycarbonyl-l-prolyl]-4-(2-chloro-5-methylphenoxy)piperidineYield 100.6%

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-butoxycarbonylglycylamino)-N-tert-butoxycarbonyl-L-proline (Compound D103 (B), 200 mg), 4-(2-chloro-5-methylphenoxy)piperidine (117 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 14 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 evaporated in vacuo. The residue was washed with hexane to give the titled compound (309 mg) as a white foam: 1H NMR (400 MHz, CDCl3) δ 1.43-1.46 (18H), 1.89 (br s, 4H), 2.16 (br s, 2H), 2.32 (s, 3H), 3.34-3.60 (m, 3H), 3.70-4.00 (m, 5H), 4.49 (br s, 0.5H), 4.62 (m, 2H), 4.79 (br s, 0.5H), 5.11 (br s, 1H), 6.34 (br s, 1H), 6.77 (m, 2H), and 7.24 (m, 1H). Anal. Calcd for C29H43Cl1N4O7: C, 58.53; H, 7.28; N, 9.41; Cl, 5.96. Found: C, 58.21; H, 7.35; N, 9.25; Cl, 6.03; IR (KBr) 3319, 2978, 2933, 1699, 1666, 1404, 1252, 1165, 1061 cm−1; mass spectrum (EI+) m/e 594 (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. customthe organic layer was evaporated in vacuo
  5. washThe residue was washed with hexane

Sources & evidence

ORD record
ord-434768722fa643e7bb8566dfc378002e
Source dataset
uspto-grants-2002_06
Patent number
US06399629B1

Reaction notes

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