4-Methylmorpholine → Methyl N2-(tert-butoxycarbonyl)-N5,N5-bis(2-((tert-butoxycarbonyl)amino)ethyl)-L-glutaminate

HRID 1425906Notes

Reaction equation

HRID 1425906 reaction equation
CN1CCOCC1.[C:8]([O:12][C:13]([NH:15][C@H:16]([C:22]([O:24][CH3:25])=[O:23])[CH2:17][CH2:18][C:19]([OH:21])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].[C:26]([O:30][C:31]([NH:33][CH2:34][CH2:35][NH:36][CH2:37][CH2:38][NH:39][C:40](=[O:46])[O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:32])([CH3:29])([CH3:28])[CH3:27]>C(Cl)Cl>[C:42]([O:41][C:40]([NH:39][CH2:38][CH2:37][N:36]([CH2:35][CH2:34][NH:33][C:31]([O:30][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:32])[C:19]([CH2:18][CH2:17][C@H:16]([NH:15][C:13]([O:12][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:14])[C:22]([O:24][CH3:25])=[O:23])=[O:21])=[O:46])([CH3:45])([CH3:44])[CH3:43]

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 7018754(4S)-4-(((tert-butoxy)carbonyl)amino)-5-methoxy-5-oxopentanoic acidHCID 15157893tert-butyl N-{2-[(2-{[(tert-butoxy)carbonyl]amino}ethyl)amino]ethyl}carbamate

Product 1

HCID 59366631Methyl N2-(tert-butoxycarbonyl)-N5,N5-bis(2-((tert-butoxycarbonyl)amino)ethyl)-L-glutaminateYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of CDMT (2.22 g, 12.62 mmol) in DCM (40 mL) and cooled to 0° C. was added N-methylmorpholine (1.38 mL, 12.63 mmol). The mixture was stirred for 10 min before adding (4S)-4-{[(tert-butoxy)carbonyl]amino}-5-methoxy-5-oxopentanoic acid (3.0 g, 11.48 mmol). The solution was stirred for 60 min at 0° C. The tert-butyl N-{2-[(2-{[(tert-butoxy)carbonyl]amino}ethyl)amino]ethyl}carbamate XIV was then added and the mixture stirred at room temperature overnight. The solution was washed with 1 M aq. K2CO3, 1 M aq. HCl, brine and dried over anhydrous MgSO4. The crude product was crystallized from DCM/hexane to give methyl (2S)-4-[bis(2-{[(tert-butoxy)carbonyl]amino}ethyl)carbamoyl]-2-{[(tert-butoxy)carbonyl]amino}butanoate (XV) (4.91 g, 8.98 mmol, 72% yield). 1H NMR (DMSO-d6) δ ppm 1.35-1.47 (m, 27H), 1.80-1.91 (m, 1H), 2.19-2.32 (m, 1H), 2.33-2.42 (m, 1H), 2.46-2.57 (m, 1H), 3.11-3.38 (m, 6H), 3.40-3.53 (m, 1H), 3.54-3.62 (m, 1H), 3.73 (s, 3H), 4.26-4.38 (m, 1H), 4.99-5.09 (brs, 1H), 5.31-5.46 (m, 2H); ESIMS found for C25H46N4O9 m/z 547 (M+H).

Workup

  1. stirringThe solution was stirred for 60 min at 0° C
  2. stirringthe mixture stirred at room temperature overnight
  3. washThe solution was washed with 1 M aq. K2CO3, 1 M aq. HCl, brine
  4. dry with materialdried over anhydrous MgSO4
  5. customThe crude product was crystallized from DCM/hexane

Sources & evidence

ORD record
ord-586064a691764d6bbb3f0692b1601214
Source dataset
uspto-grants-2015_01
Patent number
US08933018B2

Reaction notes

Loading…