Diisopropylethylamine → tert-butyl 2-methyl-1-((R)-1-((4S,5R)-2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxo-4-phenoxybutan-2-ylamino)-1-oxopropan-2-ylcarbamate

HRID 1036698Notes

Reaction equation

HRID 1036698 reaction equation
[NH2:1][C@H:2]([CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:3]([N:5]1[CH2:22][CH2:21][CH2:20][C@:7]2([C:11](=[O:12])[N:10]([CH3:13])[CH2:9][C@H:8]2[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:6]1)=[O:4].[C:32]([O:36][C:37]([NH:39][C:40]([CH3:45])([CH3:44])[C:41](O)=[O:42])=[O:38])([CH3:35])([CH3:34])[CH3:33].C(N(C(C)C)CC)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C(#N)C>[CH3:45][C:40]([NH:39][C:37](=[O:38])[O:36][C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:44])[C:41]([NH:1][C@H:2]([CH2:23][CH2:24][O:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:3]([N:5]1[CH2:22][CH2:21][CH2:20][C@:7]2([C:11](=[O:12])[N:10]([CH3:13])[CH2:9][C@H:8]2[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:6]1)=[O:4])=[O:42]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 71060207(4S,5R)-7-((R)-2-amino-4-phenoxybutanoyl)-2-methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one

Product 1

HCID 71060370tert-butyl 2-methyl-1-((R)-1-((4S,5R)-2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxo-4-phenoxybutan-2-ylamino)-1-oxopropan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(4S,5R)-7-((R)-2-amino-4-phenoxybutanoyl)-2-methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one (55 mg; 0.130 mmol) was solubilised in acetonitrile (0.5 ml). 2-(tert-butoxycarbonylamino)-2-methylpropanoic acid (27 mg; 0.130 mmol) was added followed by diisopropylethylamine (0.091 ml; 0.522 mmol). The solution was stirred at RT for 5 minutes before ®T3P (50% solution in ethyl acetate) (0.152 ml; 0.261 mmol) was added. The mixture was stirred overnight, then concentrated in vacuo and purified by chromatography on silica eluting with 0-10% MeOH in TBME with ammonia to yield tert-butyl 2-methyl-1-((R)-1-((4S,5R)-2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxo-4-phenoxybutan-2-ylamino)-1-oxopropan-2-ylcarbamate.

Workup

  1. additionwas added
  2. concentrationconcentrated in vacuo
  3. custompurified by chromatography on silica eluting with 0-10% MeOH in TBME with ammonia

Sources & evidence

ORD record
ord-03fce944b5f84c35a6f9470d4f2fe09d
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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