4-Methylmorpholine → Boc-Leu-Leu-Lys(Z)-Leu-Leu-OMe

HRID 849690Notes

Reaction equation

HRID 849690 reaction equation
CN1CCOCC1.[NH2:8][C@H:9]([C:25]([NH:27][C@H:28]([C:33]([NH:35][C@H:36]([C:41]([O:43][CH3:44])=[O:42])[CH2:37][CH:38]([CH3:40])[CH3:39])=[O:34])[CH2:29][CH:30]([CH3:32])[CH3:31])=[O:26])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16].Cl.C1C=CC2N(O)N=NC=2C=1.[NH:56]([C:73]([O:75][C:76]([CH3:79])([CH3:78])[CH3:77])=[O:74])[C@H:57]([C:62]([NH:64][C@H:65]([C:70](O)=[O:71])[CH2:66][CH:67]([CH3:69])[CH3:68])=[O:63])[CH2:58][CH:59]([CH3:61])[CH3:60].CC(C)N=C=NC(C)C>CN(C=O)C.O>[NH:56]([C:73]([O:75][C:76]([CH3:79])([CH3:78])[CH3:77])=[O:74])[C@H:57]([C:62]([NH:64][C@H:65]([C:70]([NH:8][C@H:9]([C:25]([NH:27][C@H:28]([C:33]([NH:35][C@H:36]([C:41]([O:43][CH3:44])=[O:42])[CH2:37][CH:38]([CH3:39])[CH3:40])=[O:34])[CH2:29][CH:30]([CH3:31])[CH3:32])=[O:26])[CH2:10][CH2:11][CH2:12][CH2:13][NH:14][C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16])=[O:71])[CH2:66][CH:67]([CH3:68])[CH3:69])=[O:63])[CH2:58][CH:59]([CH3:61])[CH3:60]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 12734DiisopropylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 7019882(S)-2-((S)-2-((tert-Butoxycarbonyl)amino)-4-methylpentanamido)-4-methylpentanoic acidHCID 131721603H-Lys(Z)-Leu-Leu-OMe.HCl

Product 1

HCID 12020547Boc-Leu-Leu-Lys(Z)-Leu-Leu-OMeYield 86.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
19 °C

Procedure

4-Methylmorpholine (2.53 g, 25 mmol) was added to a solution of H-Lys(Z)-Leu-Leu-OMe·HCl (13.93 g, 25 mmol) in DMF (85.0 g) at 10° C. HOBt (3.38 g, 25 mmol), Boc-Leu-Leu-OH (8.61 g, 25 mmol) and DIC (3.47 g, 27.5 mmol) were added over 30 min at 8-10° C. An additional portion of DMF (5.0 g) was added and the reaction was kept at 8-10° C. for 16 h. The reaction was stirred at 18-20° C. for 3 h, cooled to 5-10° C. and treated with H2O (130.0 g). A solid precipitated at 25° C. which was filtered, washed with H2O and recrystallized from MeOH and H2O to give Boc-Leu-Leu-Lys(Z)-Leu-Leu-OMe (SEQ. ID No. 2) (18.3 g, 86.4%).

Workup

  1. temperaturecooled to 5-10° C.
  2. customA solid precipitated at 25° C. which
  3. filtrationwas filtered
  4. washwashed with H2O
  5. customrecrystallized from MeOH and H2O

Sources & evidence

ORD record
ord-53f7b4df04034305934cafec1fd80af7
Source dataset
uspto-grants-2000_01
Patent number
US06013764

Reaction notes

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