Dimethylformamide → HCID 70815243, compound

HRID 80579Notes

Reaction equation

HRID 80579 reaction equation
C([C@H]([C@@H](C(O)=O)O)O)(O)=O.[NH2:11][C@@H:12]([C:15]1[CH:16]=[C:17]([CH:25]=[CH:26][N:27]=1)[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13][CH3:14].CN(C)C=O.C(N(CC)CC)C.[Cl:40][C:41]1[CH:42]=[CH:43][C:44]([O:80][CH3:81])=[C:45]([CH:79]=1)[CH2:46][C@H:47]1[C:53](=[O:54])[N:52]([C:55](OC2C=CC=CC=2Cl)=[O:56])[CH2:51][C:50](=[O:65])[N:49]([CH2:66][C:67]2[C:72]([O:73][CH3:74])=[CH:71][C:70]([O:75][CH3:76])=[CH:69][C:68]=2[O:77][CH3:78])[CH2:48]1>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Cl:40][C:41]1[CH:42]=[CH:43][C:44]([O:80][CH3:81])=[C:45]([CH:79]=1)[CH2:46][C@H:47]1[C:53](=[O:54])[N:52]([C:55]([NH:11][C@@H:12]([C:15]2[CH:16]=[C:17]([CH:25]=[CH:26][N:27]=2)[C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[CH2:13][CH3:14])=[O:56])[CH2:51][C:50](=[O:65])[N:49]([CH2:66][C:67]2[C:68]([O:77][CH3:78])=[CH:69][C:70]([O:75][CH3:76])=[CH:71][C:72]=2[O:73][CH3:74])[CH2:48]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 66935304(6R)-2-chlorophenyl 6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepan-1-carboxylateHCID 66935362HCID 66935362, compound

Product 1

HCID 70815243HCID 70815243, compoundYield 71.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To the compound 5105 described in WO 06-059801A, that is, tert-butyl 2-[(1R)-1-aminopropyl]-isonicotinate D-tartrate (157 mg) in an N,N-dimethylformamide (1.5 ml) solution, triethylamine (0.113 ml) was added under ice cooling, and the mixture was stirred at that temperature for 5 minutes. To the reaction solution, the compound S141C described in WO 06-059801A, that is, (6R)-2-chlorophenyl 6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepane-1-carboxylate (250 mg) and 4-dimethylaminopyridine (49 mg) were added, and the mixture was stirred at 0° C. for 18 hours. The reaction solution was diluted with ethyl acetate, then was successively washed with saturated aqueous ammonium chloride solution and brine. The organic layer was dried over anhydrous sodium sulfate, then was concentrated. The residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate=1/1 to 1/2) to obtain tert-butyl 2-[(1R)-1-({[(6R)-6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepan-1-yl]carbonyl}amino)propyl]isonicotinate (compound S39a) (210 mg).

Workup

  1. stirringthe mixture was stirred at 0° C. for 18 hours
  2. washwas successively washed with saturated aqueous ammonium chloride solution and brine
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. concentrationwas concentrated
  5. customThe residue was purified by flash column chromatography (silica gel, hexane/ethyl acetate=1/1 to 1/2)

Sources & evidence

ORD record
ord-6cd33210deed409195bf59353f72167e
Source dataset
uspto-grants-2014_09
Patent number
US08846660B2

Reaction notes

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