4-Methylmorpholine → N-(N-(N-(N-((1,1-dimethyl)ethoxycarbonyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [9alpha-fluoro-11beta,21-dihydroxy-16beta-methyl-3,20-dioxo-17-valeroyloxy-pregna-1,4-dien-21-yl] ester

HRID 53070Notes

Reaction equation

HRID 53070 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]([CH3:46])[C@:23]2([O:39][C:40](=[O:45])[CH2:41][CH2:42][CH2:43][CH3:44])[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@@:10]1([F:49])[C@:11]1([CH3:48])[C:16]([CH2:17][CH2:18]2)=[CH:15][C:14](=[O:47])[CH:13]=[CH:12]1.[NH:50]([C:68]([O:70][C:71]([CH3:74])([CH3:73])[CH3:72])=[O:69])[C@H:51]([C:53]([NH:55][C@H:56]([C:58]([N:60]1[CH2:67][CH2:66][CH2:65][C@H:61]1[C:62](O)=[O:63])=[O:59])[CH3:57])=[O:54])[CH3:52].CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[F:49][C@:10]12[C@@H:9]([OH:8])[CH2:37][C@@:36]3([CH3:38])[C@@H:20]([CH2:21][C@H:22]([CH3:46])[C@:23]3([O:39][C:40](=[O:45])[CH2:41][CH2:42][CH2:43][CH3:44])[C:24](=[O:35])[CH:25]([O:27][C:28](=[O:34])[C@H:29]([CH:30]([CH3:32])[CH3:31])[NH:33][C:62](=[O:63])[C@@H:61]3[CH2:65][CH2:66][CH2:67][N:60]3[C:58](=[O:59])[C@H:56]([CH3:57])[NH:55][C:53](=[O:54])[C@H:51]([CH3:52])[NH:50][C:68]([O:70][C:71]([CH3:72])([CH3:73])[CH3:74])=[O:69])[OH:26])[C@@H:19]1[CH2:18][CH2:17][C:16]1[C@:11]2([CH3:48])[CH:12]=[CH:13][C:14](=[O:47])[CH:15]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 11902955Boc-ala-ala-pro-OHHCID 131719968(2S)-2-Amino-3-methyl-butyric acid [11beta,21-dihydroxy-3,20-dioxo-9-fluoro-16beta-methyl-17-valeroyloxy-pregna-1,4-dien-21-yl] ester trifluoroacetate

Product 1

HCID 131719967N-(N-(N-(N-((1,1-dimethyl)ethoxycarbonyl)-L-alanyl)-L-alanyl)-L-prolyl)-L-valine [9alpha-fluoro-11beta,21-dihydroxy-16beta-methyl-3,20-dioxo-17-valeroyloxy-pregna-1,4-dien-21-yl] esterYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1.04 g (1.50 mmol) of H-Val-O-BMV x TFA (Example 37), 500 mg (1.40 mmol) of Boc-Ala-Ala-Pro-OH and 168 mg (1.40 mmol) of Nhydroxybenzotriazole 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 20 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 806 mg(63% ) of N-(N-(N-(N-((1,1-dimethyl)ethoxycarbonyl)-L-alanyl) -L-alanyl)-L-prolyl)-L-valine [9α-fluoro-11β,21-dihydroxy-16β-methyl-3,20-dioxo-17-valeroyloxy-pregna-1,4-dien-21-yl ] ester. Crystallization from dichloromethane/diisopropyl ether 542 mg (42%).

Workup

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

Sources & evidence

ORD record
ord-397a62ebd1fc4a77a6e0aea178561e5d
Source dataset
uspto-grants-1997_04
Patent number
US05616573

Reaction notes

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