Diisopropylethylamine → tert-butyl 1-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-3-phenyl-2,6-diazaspiro[3.5]nonan-6-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate

HRID 1036679Notes

Reaction equation

HRID 1036679 reaction equation
[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](=[O:27])[C:16]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([CH3:18])[CH3:17])[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][N:29]1[CH:32]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:31]2([CH2:43][CH2:42][CH2:41][NH:40][CH2:39]2)[C:30]1=[O:44].CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C=O)C.O>[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](=[O:27])[C:16]([NH:19][C:20](=[O:21])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:18])[CH3:17])[C:11]([N:40]1[CH2:41][CH2:42][CH2:43][C:31]2([C:30](=[O:44])[N:29]([CH3:28])[CH:32]2[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:39]1)=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 10894202(R)-3-(Benzyloxy)-2-(2-((tert-butoxycarbonyl)amino)-2-methylpropanamido)propanoic acid2×HCID 71060408Rac-2-methyl-3-phenyl-2,6-diazaspiro[3.5]nonan-1-one2×

Product 1

HCID 71060399tert-butyl 1-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-3-phenyl-2,6-diazaspiro[3.5]nonan-6-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture comprising (R)-3-(benzyloxy)-2-(2-(tert-butoxycarbonylamino)-2-methyl propanamido)propanoic acid (Intermediate 3A) (300 mg, 0.789 mmol), rac-2-methyl-3-phenyl-2,6-diazaspiro[3.5]nonan-1-one (Intermediate 2A) (182 mg, 0.789 mmol) and DIPEA (0.551 ml, 3.15 mmol) in DMF (4 ml) was treated with ®T3P (amide coupling agent 50% in DMF, 0.460 ml, 1.577 mmol) and stirred at RT for 17 hours. The reaction mixture was diluted with water (5 ml) and extracted with EtOAc. The organic portion was dried (MgSO4) and concentrated in vacuo. Purification of the crude product by chromatography on silica eluting with 1% MeOH in DCM afforded the title compound;

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic portion was dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customPurification of the crude product by chromatography on silica eluting with 1% MeOH in DCM

Sources & evidence

ORD record
ord-8169c98245a34dc9b2195b3264503111
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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