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

HRID 1036681Notes

Reaction equation

HRID 1036681 reaction equation
[CH:1]([N:4]1[CH2:8][CH:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2([CH2:19][CH2:18][CH2:17][NH:16][CH2:15]2)[C:5]1=[O:20])([CH3:3])[CH3:2].[C:21]([O:25][C:26]([NH:28][C:29]([CH3:48])([CH3:47])[C:30]([NH:32][C@H:33]([CH2:37][C:38]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[NH:40][CH:39]=1)[C:34](O)=[O:35])=[O:31])=[O:27])([CH3:24])([CH3:23])[CH3:22].CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C=O)C.O>[NH:40]1[C:41]2[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:38]([CH2:37][C@@H:33]([NH:32][C:30](=[O:31])[C:29]([NH:28][C:26](=[O:27])[O:25][C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:48])[CH3:47])[C:34]([N:16]2[CH2:17][CH2:18][CH2:19][C:6]3([C:5](=[O:20])[N:4]([CH:1]([CH3:3])[CH3:2])[CH2:8][CH:7]3[C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[CH2:15]2)=[O:35])=[CH:39]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 15895387(R)-2-(2-((tert-Butoxycarbonyl)amino)-2-methylpropanamido)-3-(1H-indol-3-yl)propanoic acid2×HCID 710605902-Isopropyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one

Product 1

HCID 71060502tert-butyl 1-((2R)-3-(1H-indol-3-yl)-1-(2-isopropyl-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 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture comprising 2-isopropyl-4-phenyl-2,7-diazaspiro[4.5]decan-1-one (ASW MedChem) (278 mg, 0.899 mmol), (R)-2-(2-(tert-butoxycarbonylamino)-2-methylpropanamido)-3-(1H-indol-3-yl)propanoic acid (Intermediate 3C) (350 mg, 0.899 mmol) and DIPEA (0.628 ml, 3.59 mmol) in DMF (4 ml) was treated with ®T3P (50% in DMF, 0.525 ml, 1.797 mmol) and stirred at RT for 2 h 20 min. 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 Purification of the crude product by chromatography on silica eluting with 1% MeOH in DCM

Sources & evidence

ORD record
ord-df1e6b81400544d7858c8555d86c9157
Source dataset
uspto-grants-2013_10
Patent number
US08546416B2

Reaction notes

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