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

HRID 1036675Notes

Reaction equation

HRID 1036675 reaction equation
[CH3:1][N:2]([CH3:23])[C:3](=[O:22])[CH2:4][N:5]1[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C@:7]2([CH2:20][CH2:19][CH2:18][NH:17][CH2:16]2)[C:6]1=[O:21].CN(C)C(=O)CN1C[C@@H](C2C=CC=CC=2)[C@@]2(CCCNC2)C1=O.[CH2:47]([O:54][CH2:55][C@@H:56]([NH:60][C:61](=[O:73])[C:62]([NH:65][C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])([CH3:64])[CH3:63])[C:57](O)=[O:58])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1.CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>C(#N)C>[CH2:47]([O:54][CH2:55][C@@H:56]([NH:60][C:61](=[O:73])[C:62]([NH:65][C:66](=[O:67])[O:68][C:69]([CH3:72])([CH3:71])[CH3:70])([CH3:64])[CH3:63])[C:57]([N:17]1[CH2:18][CH2:19][CH2:20][C:7]2([C:6](=[O:21])[N:5]([CH2:4][C:3]([N:2]([CH3:23])[CH3:1])=[O:22])[CH2:9][CH:8]2[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:16]1)=[O:58])[C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 10894202(R)-3-(Benzyloxy)-2-(2-((tert-butoxycarbonyl)amino)-2-methylpropanamido)propanoic acid2×HCID 71060309(4R,5S)-N,N-dimethyl-2-(1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-2-yl)acetamideHCID 71060312(4S,5R)-N,N-Dimethyl-2-(1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-2-yl)acetamide2×

Product 1

HCID 71060339tert-butyl 1-((2R)-3-(benzyloxy)-1-(2-(2-(dimethylamino)-2-oxoethyl)-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 6342AcetonitrileSolvent

Procedure

A racemic mixture of (4R,5S)—N,N-dimethyl-2-(1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-2-yl)acetamide and (4S,5R)—N,N-Dimethyl-2-(1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-2-yl)acetamide (Intermediate 1D) (193 mg; 0.612 mmol) was solubilised in acetonitrile (3 ml). (R)-3-Benzyloxy-2-(2-tert-butoxycarbonylamino-2-methylpropionylamino)-propionic acid (Intermediate 3A) (233 mg; 0.612 mmol) was treated with DIPEA (0.427 ml; 2.448 mmol) and ®T3P (50% in EtOAc), (0.714 ml; 1.224 mmol). The mixture was stirred at RT for 2 hours and concentrated in vacuo. The crude residue was solubilised in ethyl acetate and washed with water (3×50 ml). The organics were washed with brine, dried with magnesium sulfate, filtered and concentrated to yield the title compound.

Workup

  1. concentrationconcentrated in vacuo
  2. washwashed with water (3×50 ml)
  3. washThe organics were washed with brine
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-d77eb099b58d4bb68fd6a7ddc17a5949
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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