Ethylmorpholine → (N-benzyloxycarbonyl-L-isoleucyl)-N-(4-bromo-2-picolinoylpheny)-glycinamide

HRID 442038

Reaction equation

HRID 442038 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:17]([OH:19])=O)[C@H:13]([CH2:15][CH3:16])[CH3:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(OC(Cl)=O)C(C)C.C(N1CCOCC1)C.Cl.Cl.[NH2:38][CH2:39][C:40]([NH:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[C:49](=[O:57])[C:50]1[CH:55]=[C:54]([Br:56])[CH:53]=[CH:52][N:51]=1)=[O:41]>CN(C)C=O.O1CCCC1>[CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:17]([NH:38][CH2:39][C:40]([NH:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[C:49](=[O:57])[C:50]1[CH:55]=[C:54]([Br:56])[CH:53]=[CH:52][N:51]=1)=[O:41])=[O:19])[C@H:13]([CH2:15][CH3:16])[CH3:14])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 7525Ethylmorpholine2×HCID 62365Isobutyl chloroformateHCID 2724772N-[(Phenylmethoxy)carbonyl]-L-isoleucineHCID 705599642-amino-N-(4-bromo-2-picolinoylphenyl)-acetamide dihydrochloride

Product 1

HCID 70560342(N-benzyloxycarbonyl-L-isoleucyl)-N-(4-bromo-2-picolinoylpheny)-glycinamideYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

3.18 g. of N-benzyloxycarbonyl-L-isoleucine were dissolved in 25 ml. of dry tetrahydrofuran and cooled to -10° C. 1.57 ml. of isobutylchloroformate and 1.52 l ml. of N-ethylmorpholine were added and the resulting solution was stirred at -10° C. for 20 minutes. 4.24 g. of 2-amino-N-(4-bromo-2-picolinoylphenyl)-acetamide dihydrochloride, prepared as described in part (A) (i) of Example 1, were added and the resulting suspension was cooled to -20° C. 3.13 ml. of N-ethylmorpholine in 25 ml. of dimethylformamide were added to the vigorously stirred suspension over a period of 0.5 hour. The resulting mixture was stirred at -20° C. for a further 40 minutes and left at room temperature overnight. The product was worked up in a manner analogous to that described in part (A) (ii) of Example 1. Recrystallisation from ethanol yielded 4.2 g (60%) of (N-benzyloxycarbonyl-L-isoleucyl)-N-(4-bromo-2-picolinoylpheny)-glycinamide of melting point 174°-176° C.

Workup

  1. additionwere added
  2. temperaturethe resulting suspension was cooled to -20° C
  3. stirringThe resulting mixture was stirred at -20° C. for a further 40 minutes
  4. waitleft at room temperature overnight
  5. customRecrystallisation from ethanol

Sources & evidence

ORD record
ord-49fdab5aa8124218b447a7c94e8da547
Source dataset
uspto-grants-1977_08
Patent number
US04044017

Linked notes

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