2-Dimethylaminopyridine → tert-butyl 4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepan-1-yl]carbonyl}amino)propyl]-2-nitrobenzoate

HRID 554830Notes

Reaction equation

HRID 554830 reaction equation
[C:1]([O:5]C(OC(OC(C)(C)C)=O)=O)(C)(C)C.CN(C1C=CC=CN=1)C.[NH2:25][C@@H:26]([C:29]1[CH:41]=[CH:40][C:32]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[C:31]([N+:42]([O-:44])=[O:43])[CH:30]=1)[CH2:27][CH3:28].[Cl:45][C:46]1[CH:47]=[CH:48][C:49]([O:75][CH3:76])=[C:50]([CH:74]=1)[CH2:51][C@H:52]1[CH2:58][N:57]([CH2:59][C:60]2[C:65]([O:66][CH3:67])=[CH:64][C:63]([O:68][CH3:69])=[CH:62][C:61]=2[O:70][CH3:71])[C:56](=[O:72])[CH2:55][NH:54][C:53]1=[O:73].CC(C)([O-])C.[K+]>C(#N)C.O1CCCC1.C(O)(=O)C>[Cl:45][C:46]1[CH:47]=[CH:48][C:49]([O:75][CH3:76])=[C:50]([CH:74]=1)[CH2:51][C@@H:52]1[C:53](=[O:73])[N:54]([C:1]([NH:25][C@@H:26]([C:29]2[CH:41]=[CH:40][C:32]([C:33]([O:35][C:36]([CH3:38])([CH3:39])[CH3:37])=[O:34])=[C:31]([N+:42]([O-:44])=[O:43])[CH:30]=2)[CH2:27][CH3:28])=[O:5])[CH2:55][C:56](=[O:72])[N:57]([CH2:59][C:60]2[C:61]([O:70][CH3:71])=[CH:62][C:63]([O:68][CH3:69])=[CH:64][C:65]=2[O:66][CH3:67])[CH2:58]1

Participants

9

Reactant 5

HCID 218852-DimethylaminopyridineHCID 90495Di-tert-butyl dicarbonateHCID 23665647Potassium tert-butoxideHCID 66934844tert-butyl 4-((1R)-1-aminopropyl)-2-nitrobenzoateHCID 66935303(6S)-6-(5-chloro-2-methoxybenzyl)-1-(2,4,6-trimethoxybenzyl)-1,4-diazepan-2,5-dione

Product 1

HCID 67462760tert-butyl 4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepan-1-yl]carbonyl}amino)propyl]-2-nitrobenzoateYield 805.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of di-tert-butyldicarbonate (7.1 g) and dimethylaminopyridine (3.8 g) in acetonitrile (8 ml) cooled at −10° C., a solution of tert-butyl 4-((1R)-1-aminopropyl)-2-nitrobenzoate (8.7 g) in an acetonitrile (0.9 ml) was added at −10° C., and the mixture was stirred for 15 minutes. Next, the reaction solution was deaerated at an internal pressure of 60 to 100 mmHg for 1 hour, and then (6S)-6-(5-chloro-2-methoxybenzyl)-1-(2,4,6-trimethoxybenzyl)-1,4-diazepan-2,5-dione (1.3 g) was added. Next 1N solution of potassium tert-butoxide in tetrahydrofuran (0.53 ml) was dropwisely added to the mixture. After the end of the addition, acetic acid (2 ml) was added to the reaction solution, the mixture was concentrated in vacuo. Ethyl acetate was added to the obtained residue, and the mixture was washed with water. Then the organic layer was dried over anhydrous magnesium sulfate, and the solvent was distilled off in vacuo. The concentrated residue was purified with silica gel chromatography to obtain the title compound (17.4 g) as an oily substance. The 1H-NMR data matches those of Example 329.

Workup

  1. waitNext, the reaction solution was deaerated at an internal pressure of 60 to 100 mmHg for 1 hour
  2. additionwas added to the reaction solution
  3. concentrationthe mixture was concentrated in vacuo
  4. additionEthyl acetate was added to the obtained residue
  5. washthe mixture was washed with water
  6. dry with materialThen the organic layer was dried over anhydrous magnesium sulfate
  7. distillationthe solvent was distilled off in vacuo
  8. customThe concentrated residue was purified with silica gel chromatography

Sources & evidence

ORD record
ord-36b88a2ab2324e579e38eeb8de5f4dc7
Source dataset
uspto-grants-2011_11
Patent number
US08049006B2

Reaction notes

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