1,2-Dichloroethane → N-[1(R)-[(2,3-Dihydro-spiro[1H-indene-1,4'-piperdin]-1'-yl)carbonyl]-3-phenylpropyl]-2-[(1,1-dimethylethoxy)carbonyl]amino-2-methylpropanamide

HRID 1902160Notes

Reaction equation

HRID 1902160 reaction equation
C(O[C:6]([NH:8][C@H:9]([CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10]([OH:12])=O)=[O:7])(C)(C)C.Cl.[NH:22]1[CH2:27][CH2:26][C:25]2([C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][CH2:28]2)[CH2:24][CH2:23]1.CN1CCOCC1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.[H][H].[C:59]([O:63][C:64]([NH:66][C:67](C)([CH3:71])[C:68](O)=O)=[O:65])([CH3:62])([CH3:61])[CH3:60]>C(Cl)(Cl)Cl.C(O)C.[Pd]>[N:22]1([C:10]([C@H:9]([NH:8][C:6](=[O:7])[C:67]([NH:66][C:64]([O:63][C:59]([CH3:61])([CH3:60])[CH3:62])=[O:65])([CH3:71])[CH3:68])[CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])[CH2:27][CH2:26][C:25]2([C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][CH2:28]2)[CH2:24][CH2:23]1

Participants

11

Reactant 7

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 2755954Boc-D-homophenylalanineHCID 225093272,3-Dihydrospiro[indene-1,4'-piperidine] hydrochlorideHCID 178418361HCID 178418361, compound

Product 1

HCID 67613101N-[1(R)-[(2,3-Dihydro-spiro[1H-indene-1,4'-piperdin]-1'-yl)carbonyl]-3-phenylpropyl]-2-[(1,1-dimethylethoxy)carbonyl]amino-2-methylpropanamide

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6212ChloroformSolvent2×

Procedure

To a solution of (2R)-2-[(tert-butoxycarbonyl)amino]-4-phenyl-butanoic acid (0.1 g, 0.37 mmol), 2,3-dihydro-spiro[1H-indene-1,4'-piperdine]hydrochloride (0.10 g, 0.45 mmol), N-methyl-morpholine (0.1 mL, 2 eq), and HOBT (1 eq) in 3mL of chloroform was added and EDC (0.14 g, 0.73 mmol) and stirred at RT overnight. The work-up and isolation is the same as Example 77, Step C. The crude product was purified on silica gel using 20% ethyl acetate in hexane. This material (0.25 g, 0.56 mmol) was hydrogenated in ethyl alcohol using catalytic amount of 10% Pd/C and a hydrogen balloon at room temperature overnight. The catalyst was filtered off and washed with MeOH. Upon evaporation of the solvent the reduced material was obtained. This material was deprotected as described in Example 77, Step C. This intermediate was coupled to 2-(tert-butoxycarbonyl)amino-2-methyl-propanoic acid as illustrated in Example 77, Step C. The title compound was obtained by purification of the residue on silica gel using 5% MeOH in CHCl3.

Workup

  1. customThe crude product was purified on silica gel using 20% ethyl acetate in hexane
  2. customat room temperature
  3. customovernight
  4. filtrationThe catalyst was filtered off
  5. washwashed with MeOH
  6. customUpon evaporation of the solvent the reduced material
  7. customwas obtained

Sources & evidence

ORD record
ord-744a99aee1844ffcbdbe9214660c6ff6
Source dataset
uspto-grants-1996_11
Patent number
US05578593

Reaction notes

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