1,2-Dichloroethane → HCID 22867455, compound

HRID 1902150Notes

Reaction equation

HRID 1902150 reaction equation
[CH3:1][C:2]([CH3:28])([O:4][C:5]([NH:7][C:8]([CH3:27])([CH3:26])[C:9]([NH:11][C@H:12]([CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][CH:18]=1)[C:13]([OH:15])=O)=[O:10])=[O:6])[CH3:3].Cl.[NH:30]1[CH2:35][CH2:34][C:33]2([C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:37]=[CH:36]2)[CH2:32][CH2:31]1.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl.Cl>ClCCl.[Cl-].[Na+].O>[N:30]1([C:13]([C@H:12]([NH:11][C:9](=[O:10])[C:8]([NH:7][C:5]([O:4][C:2]([CH3:3])([CH3:28])[CH3:1])=[O:6])([CH3:26])[CH3:27])[CH2:16][C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][CH:18]=2)=[O:15])[CH2:35][CH2:34][C:33]2([C:43]3[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:37]=[CH:36]2)[CH2:32][CH2:31]1

Participants

9

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 15895387(R)-2-(2-((tert-Butoxycarbonyl)amino)-2-methylpropanamido)-3-(1H-indol-3-yl)propanoic acidHCID 22509344Spiro[indene-1,4'-piperidine] hydrochloride

Product 1

HCID 22867455HCID 22867455, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a stirred solution of α(R)-[[2-[[(1,1-dimethylethoxy)carbonyl]amino]-2,2-dimethyl-1-oxoethyl]amino]-1H-indole-3-propanoic acid (50 mg, 0.13 mmol), (Example 4, Step D) spiro[1H-indene-1,4'-piperidine]hydrochloride (28.5 mg, 0.13 mmol) (Chambers, M. et al, J. Med. Chem. 1992, 35, 2033-2039), HOBT (17.3 mg, 0.13 mmol) and N-methylmorpholine (14.1 μL, 0.13 mmol) in dichloromethane (5 mL) at room temperature was added EDC (49.3 mg, 0.26 mmol). The reaction mixture was stirred for four hours and poured into a mixture of brine (10 mL) and HCl (3N, 1 mL). The mixture was extracted with ethyl acetate (20 mL) and the organic extract was dried (MgSO4) and evaporated. The residue was purified by silica gel column eluting with a solvent gradient of 40-60% ethyl acetate in hexane to give the product (63.6 mg, 89%).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (20 mL)
  2. extractionthe organic extract
  3. dry with materialwas dried (MgSO4)
  4. customevaporated
  5. customThe residue was purified by silica gel column
  6. washeluting with a solvent gradient of 40-60% ethyl acetate in hexane

Sources & evidence

ORD record
ord-c2aca83185a147a499f7f18120de2763
Source dataset
uspto-grants-1996_11
Patent number
US05578593

Reaction notes

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