4-Methylmorpholine → HCID 131720933, compound

HRID 355584Notes

Reaction equation

HRID 355584 reaction equation
[NH:1]([C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32])[C@H:2]([C:6]([NH:8][C@H:9]([C:13]([N:15]([CH3:30])[C@H:16]([C:20]([N:22]1[CH2:29][CH2:28][CH2:27][C@H:23]1[C:24](O)=[O:25])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:12])[CH3:11])=[O:7])[CH:3]([CH3:5])[CH3:4].[NH:41]1[CH2:66][CH2:65][CH2:64][C@H:42]1[C:43]([NH:45][C@H:46]([C:50]([NH:52][C@H:53]([C:61]([NH2:63])=[O:62])[CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:51])[CH:47]([CH3:49])[CH3:48])=[O:44].CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>ClCCl>[NH:1]([C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32])[C@H:2]([C:6]([NH:8][C@H:9]([C:13]([N:15]([CH3:30])[C@H:16]([C:20]([N:22]1[CH2:29][CH2:28][CH2:27][C@H:23]1[C:24]([N:41]1[CH2:66][CH2:65][CH2:64][C@H:42]1[C:43]([NH:45][C@H:46]([C:50]([NH:52][C@H:53]([C:61]([NH2:63])=[O:62])[CH2:54][C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)=[O:51])[CH:47]([CH3:48])[CH3:49])=[O:44])=[O:25])=[O:21])[CH:17]([CH3:19])[CH3:18])=[O:14])[CH:10]([CH3:11])[CH3:12])=[O:7])[CH:3]([CH3:4])[CH3:5]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 10507094HCID 10507094, compoundHCID 131720934HCID 131720934, compound

Product 1

HCID 131720933HCID 131720933, compoundYield 84.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

25 g (43.3 mmol) Z-Val-Val-MeVal-Pro-OH and 15.59 g (43.3 mmol) H-Pro-Val-Phe-NH2 were suspended in 430 ml of dry dichloromethane. After cooling to 0° C., 5.81 ml (52 mmol) N-methylmorpholine, 1.97 g (15 mmol) HOBt and 8.33 g (43.3 mmol) EDCI were added and the reaction mixture stirred overnight at room temperature. The solvents were evaporated, the residue dissolved in 640 ml dichloromethane and thoroughly washed with saturated aqueous NaHCO3 solution (4×), water (1×), 5% citric acid (3×) and saturated NaCl solution. The organic phase was dried over sodium sulfate and evaporated to dryness to yield 33.04 g of the product. The crude product was chromatographed on a silica gel column with 20% MeOH/Hexane. 18.32 g of the desired product were obtained.

Workup

  1. customThe solvents were evaporated
  2. dissolutionthe residue dissolved in 640 ml dichloromethane
  3. washthoroughly washed with saturated aqueous NaHCO3 solution (4×), water (1×), 5% citric acid (3×) and saturated NaCl solution
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-94fbf39bf2a044369d6c90a40ab8d80b
Source dataset
uspto-grants-1998_11
Patent number
US05831002

Reaction notes

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