1,2-Dichloroethane → N-{[7-(4-t-Butoxycarbonylpiperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetyl}-3(S)-(3-pyridyl)-beta-alanine ethyl ester

HRID 862674Notes

Reaction equation

HRID 862674 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:23]=[C:22]3[C:17]([CH2:18][CH2:19][N:20]([CH2:25][C:26](O)=[O:27])[C:21]3=[O:24])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[NH2:31][C@H:32]([C:39]1[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=1)[CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[Li+].[OH-]>CN(C=O)C.CCOC(C)=O.O.CO>[CH2:37]([O:36][C:34](=[O:35])[CH2:33][C@@H:32]([C:39]1[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=1)[NH:31][C:26](=[O:27])[CH2:25][N:20]1[CH2:19][CH2:18][C:17]2[C:22](=[CH:23][C:14]([N:11]3[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12]3)=[CH:15][CH:16]=2)[C:21]1=[O:24])[CH3:38]

Participants

11

Reactant 6

HCID 111,2-DichloroethaneHCID 3939Lithium HydroxideHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 11794693[7-(4-t-Butoxycarbonylpiperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetic acidHCID 44891224Ethyl (3S)-3-amino-3-(pyridin-3-yl)propanoate--hydrogen chloride (1/2)

Product 1

HCID 10698208N-{[7-(4-t-Butoxycarbonylpiperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetyl}-3(S)-(3-pyridyl)-beta-alanine ethyl ester

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of [7-(4-t-butoxycarbonylpiperazin-1-yl)-3,4-dihydro-1(1H)-isoquinolinone-2-yl]acetic acid (1-5) (195 mg, 0.5 mmol), ethyl 3-amino-3(S)-(3-pyridyl)propionate dihydrochloride (1-6) (Rico et al, J. Org. Chem. 1993, vol. 58, p. 7948; 127 mg, 0.55 mmol), EDC (105 mg, 0.55 mmol), HOBT (74 mg, 0.55 mmol) and 4-methylmorpholine (0.12 mL, 1.1 mmol) in DMF (5 mL) was stirred at room temperature for 16 hours. The mixture was diluted with EtOAc and water and the pH adjusted to ~pH 7 with 1N LiOH. The solution was extracted with EtOAc (3×), dried (MgSO4) and the solvent removed in vacuo. Purification of the residue by column chromatography (10% MeOH in EtOAc) gave 1-7. Rf (silica, 10% MeOH in EtOAc)=0.43.

Workup

  1. extractionThe solution was extracted with EtOAc (3×)
  2. dry with materialdried (MgSO4)
  3. customthe solvent removed in vacuo
  4. customPurification of the residue by column chromatography (10% MeOH in EtOAc)
  5. customgave 1-7

Sources & evidence

ORD record
ord-36af4fea9be1455fab5b2879605146f3
Source dataset
uspto-grants-1998_02
Patent number
US05719162

Reaction notes

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