Diisopropylethylamine → tert-Butyl 1-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate

HRID 1036669Notes

Reaction equation

HRID 1036669 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[CH2:33][C@H:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@:31]2([CH2:44][CH2:43][CH2:42][NH:41][CH2:40]2)[C:30]1=[O:45].CN1C[C@@H](C2C=CC=CC=2)[C@@]2(CCCNC2)C1=O.CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>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]([CH3:24])([CH3:26])[CH3:25])([CH3:18])[CH3:17])[C:11]([N:41]1[CH2:42][CH2:43][CH2:44][C:31]2([C:30](=[O:45])[N:29]([CH3:28])[CH2:33][CH:32]2[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:40]1)=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 10894202(R)-3-(Benzyloxy)-2-(2-((tert-butoxycarbonyl)amino)-2-methylpropanamido)propanoic acid2×HCID 71060185(4S,5R)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one2×HCID 71060283(4R,5S)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one

Product 1

HCID 86674094tert-Butyl 1-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-ylamino)-2-methyl-1-oxopropan-2-ylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture comprising (R)-3-(benzyloxy)-2-(2-(tert-butoxycarbonylamino)-2-methyl propanamido)propanoic acid (Intermediate 3A) (800 mg, 2.103 mmol) and a racemic mixture of (4R,5S)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one and (4S,5R)-2-Methyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one (Intermediate 1A) (514 mg, 2.103 mmol) in DMF (10 ml) was treated with DIPEA (1.102 ml, 6.31 mmol) and ®T3P (amide coupling agent 50% in DMF, 2.455 ml, 4.21 mmol) and stirred at RT for 1 hour. The resulting mixture was concentrated in vacuo and the residue was suspended in 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 0-100% EtOAc in iso-hexane afforded the title compound as a white foam.

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. extractionextracted with EtOAc (2×100 ml)
  3. dry with materialThe combined organic extracts were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by chromatography on silica eluting with 0-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-4f9bb1fc97a94b0988174e852ca41569
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

Loading…