N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → HCID 16117472, compound

HRID 448297Notes

Reaction equation

HRID 448297 reaction equation
N12CCCN=C1CCCCC2.Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].[C:33]([NH:40][CH2:41][CH2:42][C:43](O)=[O:44])([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34]>CN(C=O)C>[C:36]([O:35][C:33](=[O:34])[NH:40][CH2:41][CH2:42][C:43](=[O:44])[NH:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24])([CH3:39])([CH3:37])[CH3:38]

Participants

5

Reactant 3

HCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 219885683-(4-(Aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride

Product 1

HCID 16117472HCID 16117472, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1,8-Diazabicyclo[5,4,0]-undec-7-ene (2.6 g, 16.8 mmol) was added to a stirred solution of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6 dione hydrochloride (2.0 g, 6.5 mmol) in DMF (100 mL). After stirring for 10 minutes, 1-hydrocybenztriazole (1.1 g, 7.8 mmol) and N—BOC-β-alanine (1.4 g, 7.1 mmol) were added. The reaction was initiated by addition of 1-[3-(dimethylamino0propyl]-3-ethylcarbodiimide hydrochloride (1.9 g, 9.7 mmol). The mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with H2O (40 mL) and CH2Cl2 (120 mL). The solid was collected to give (2-{[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-carbamoyl}-ethyl)-carbamic acid t-butyl ester (2.1 g, 73%) as a white solid: mp 203-205° C.; 1H NMR (DMSO-d6) δ 1.36 (s, 9H, 3CH3), 1.99-2.04 (m, 1H), 2.27-2.64 (m, 2H), 2.85-2.98 (m, 1H), 3.00-3.18 (m, 2H), 4.31 (d, J=5.3 Hz, 2H, CH2), 4.33-4.53 (dd, J=17.3 and 37.3 Hz, 2H, CH2), 5.10-5.17 (dd, J=4.8 and 13.1 Hz, 1H, CH), 6.79 (t, 1H, NH), 7.47-7.52 (m, 2H, Ar), 7.61-7.64 (m, 1H, Ar), 8.43 (t, J=5.3 Hz, 1H, NH), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.54, 28.19, 31.17, 35.60, 36.67, 46.15, 51.55, 77.77, 121.60, 128.24, 130.56, 131.61, 134.56, 140.04, 155.43, 168.02, 170.43, 170.95, 172.80; Anal. calcd. for C22H28N4O6: C, 59.45; H, 6.35; N, 12.60. Found: C, 59.16; H, 6.31; N, 12.50.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. concentrationThe mixture was concentrated
  3. stirringthe residue was stirred with H2O (40 mL) and CH2Cl2 (120 mL)
  4. customThe solid was collected

Sources & evidence

ORD record
ord-3771e2f82e9a426bbd8dc22aee8d1e9a
Source dataset
uspto-grants-2013_07
Patent number
US08481568B2

Reaction notes

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