4-Methylmorpholine → HCID 131719963, compound

HRID 53068Notes

Reaction equation

HRID 53068 reaction equation
FC(F)(F)C(O)=O.[OH:8][C@H:9]1[CH2:37][C@@:36]2([CH3:38])[C@@H:20]([CH2:21][C@@H:22]([CH3:39])[C@@H:23]2[C:24](=[O:35])[CH:25]([O:27][C:28](=[O:34])[C@@H:29]([NH2:33])[CH:30]([CH3:32])[CH3:31])[OH:26])[C@H:19]2[C@H:10]1[C@:11]1([CH3:42])[C:16]([C@@H:17]([F:40])[CH2:18]2)=[CH:15][C:14](=[O:41])[CH:13]=[CH:12]1.[NH:43]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[C@H:44]([C:46]([NH:48][C@H:49]([C:51]([N:53]1[CH2:60][CH2:59][CH2:58][C@H:54]1[C:55](O)=[O:56])=[O:52])[CH3:50])=[O:47])[CH3:45].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[F:40][C@@H:17]1[C:16]2[C@:11]([CH3:42])([CH:12]=[CH:13][C:14](=[O:41])[CH:15]=2)[C@@H:10]2[C@H:19]([C@H:20]3[C@:36]([CH3:38])([CH2:37][C@@H:9]2[OH:8])[C@@H:23]([C:24](=[O:35])[CH:25]([O:27][C:28](=[O:34])[C@H:29]([CH:30]([CH3:32])[CH3:31])[NH:33][C:55](=[O:56])[C@@H:54]2[CH2:58][CH2:59][CH2:60][N:53]2[C:51](=[O:52])[C@H:49]([CH3:50])[NH:48][C:46](=[O:47])[C@H:44]([CH3:45])[NH:43][C:61]([O:63][C:64]([CH3:65])([CH3:66])[CH3:67])=[O:62])[OH:26])[C@H:22]([CH3:39])[CH2:21]3)[CH2:18]1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 11902955Boc-ala-ala-pro-OHHCID 131719964HCID 131719964, compound

Product 1

HCID 131719963HCID 131719963, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

884 mg (1.50 mmol) of H-Val-O-FC x TFA (Example 31), 500 mg (1.40 mmol) of Boc-Ala-Ala-Pro-OH and 168 mg (1.40 mmol) of N-hydroxybenzotriazole are dissolved in this sequence in 50 ml of dichloromethane and 330 μl (3.00 mmol) of N-methylmorpholine is added. Then, a solution of 289 mg (1.40 mmol) of dicyclohexylcarbodiimide in 2 ml of dichloromethane is added and stirred for 2 hours at room temperature. Then, it is suctioned off from precipitated urea, the filtrate is concentrated by evaporation and filtered again. Chromatography of this amount of raw material (300 g of silica gel, hexane/acetone 1:1) yields 861 mg (76%) of N-(N-(N-(N-((1,1-dimethyl) ethoxycarbonyl) -L-alanyl) -L-alanyl)-L-prolyl)-L-valine [6α-fluoro-11β,21-dihydroxy-16α-methyl-3,20-dioxo-pregna-1,4-dien-21-yl] ester. 737 mg of pure product is obtained [one or more words missing] recrystallization from dichloromethane/diisopropyl ether.

Workup

  1. customfrom precipitated urea
  2. concentrationthe filtrate is concentrated by evaporation
  3. filtrationfiltered again

Sources & evidence

ORD record
ord-7d4fb9377319478db4202ec3bfb64698
Source dataset
uspto-grants-1997_04
Patent number
US05616573

Reaction notes

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