Water → tert-Butyl 1-((2R)-3-(benzyloxy)-1-(7-methyl-6-oxo-9-phenyl-2,7-diazaspiro[4.4]nonan-2-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate

HRID 1036702Notes

Reaction equation

HRID 1036702 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.C[CH2:29][N:30]([CH:34]([CH3:36])C)[CH:31]([CH3:33])C.C(P1(=O)OP(CCC)(=O)OP([CH2:51][CH2:52][CH3:53])(=O)O1)CC.[OH2:55]>CN(C=O)C>[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]([CH3:25])([CH3:26])[CH3:24])([CH3:18])[CH3:17])[C:11]([N:14]1[CH2:10][CH2:9][C:36]2([CH:33]([C:51]3[CH:52]=[CH:53][CH:3]=[CH:2][CH:1]=3)[CH2:31][N:30]([CH3:29])[C:34]2=[O:55])[CH2:15]1)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 10894202(R)-3-(Benzyloxy)-2-(2-((tert-butoxycarbonyl)amino)-2-methylpropanamido)propanoic acid2×

Product 1

HCID 71060634tert-Butyl 1-((2R)-3-(benzyloxy)-1-(7-methyl-6-oxo-9-phenyl-2,7-diazaspiro[4.4]nonan-2-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-3-(benzyloxy)-2-(2-(tert-butoxycarbonylamino)-2-methyl propanamido) propanoic acid (Intermediate 3A) ((280 mg, 0.736 mmol) and 2-methyl-4-phenyl-2,7-diazaspiro[4.4]nonan-1-one (step 2) (170 mg, 0.736 mmol)) in DMF (5 mL) was added DIPEA (514 uL, 2.94) and followed by ®T3P (amide coupling agent 50% in DMF, 859 uL, 1.47 mmol). The reaction was stirred at room temperature over 3 days. The resulting mixture was diluted with water (50 ml) and extracted with EtOAc (2×100 ml). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. Purification by chromatography on silica eluting with TBME:MeOH afforded the title compound

Workup

  1. extractionextracted with EtOAc (2×100 ml)
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customPurification by chromatography on silica eluting with TBME

Sources & evidence

ORD record
ord-d282ddd6eec8470ab084b951f504ec6f
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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