Hydrochloric Acid → HCID 66589482, compound

HRID 588041Notes

Reaction equation

HRID 588041 reaction equation
[N:1]1(C(OC(C)(C)C)=O)[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][N:11]2[C:16](=[O:17])[CH2:15][CH2:14][CH:13]([N:18]3[CH2:26][C:25]4[C:20](=[CH:21][CH:22]=[C:23]([CH2:27][NH:28][C:29]([NH:31][C:32]5[CH:37]=[CH:36][C:35]([CH3:38])=[C:34]([Cl:39])[CH:33]=5)=[O:30])[CH:24]=4)[C:19]3=[O:40])[C:12]2=[O:41])=[O:8])[CH2:3][CH2:2]1.Cl>CCOCC>[ClH:39].[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][N:11]2[C:16](=[O:17])[CH2:15][CH2:14][CH:13]([N:18]3[CH2:26][C:25]4[C:20](=[CH:21][CH:22]=[C:23]([CH2:27][NH:28][C:29]([NH:31][C:32]5[CH:37]=[CH:36][C:35]([CH3:38])=[C:34]([Cl:39])[CH:33]=5)=[O:30])[CH:24]=4)[C:19]3=[O:40])[C:12]2=[O:41])=[O:8])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 59443284HCID 59443284, compound

Product 1

HCID 66589482HCID 66589482, compoundYield 209.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To 1-tert-butyl 4-(3-(5-((3-(3-chloro-4-methylphenyl)ureido)methyl)-1-oxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl piperidine-1,4-dicarboxylate (300 mg, 0.44 mmol, obtained as described in previous example) was added 2 N HCl in Et2O (15 mL). The slurry was vigorously stirred for 2 h at rt. The solid was filtered, washed with copious Et2O, and dried in a vacuum oven overnight to give (3-(5-((3-(3-chloro-4-methylphenyl)ureido)methyl)-1-oxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl piperidine-4-carboxylate Hydrochloride as a white solid (285 mg, 105% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 ml/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 3.26 min (98.2%); mp: 234-236 0C; 1H NMR (DMSO-d6) δ 1.62-1.81 (m, 2H, CHH, CHH), 1.87-2.01 (m, 2H, CHH, CHH), 2.02-2.16 (m, 1H, CHH), 2.16-2.29 (m, 3H, CH3), 2.32-2.47 (m, 1H, CHH), 2.59-2.76 (m, 1H, CHH), 2.77-2.99 (m, 3H, CHH, CHH, CHH), 3.00-3.28 (m, 3H, CHH, CHH, CHH), 4.15-4.66 (m, 4H, CH2, CH2), 5.26 (dd, J=4.9, 13.2 Hz, 1H, CH), 5.55-5.80 (m, 2H, CH2O), 7.02 (t, J=5.9 Hz, 1H, NH), 7.09-7.29 (m, 2H, Ar), 7.45 (d, J=7.9 Hz, 1H, Ar), 7.53 (s, 1H, Ar), 7.62-7.82 (m, 2H, Ar), 8.41-8.96 (m, 2H, NH, NH), 9.09 (s, 1H. NH); 13C NMR (DMSO-d6) δ 18.73, 21.46, 24.31, 31.24, 37.30, 42.00, 42.73, 47.20, 52.09, 63.40, 116.31, 117.50, 121.91, 122.99, 126.97, 127.27, 130.09, 130.99, 132.96, 139.69, 142.38, 144.94, 155.21, 167.96, 170.19, 171.29, 172.20; LCMS: MH=582, 584: Anal Calcd for C29H33Cl2N5O6+1.6H2O+0.6 HCl+0.2Et2O+0.4t BuCl: C, 53.35; H, 6.05; N, 9.91; Cl, 13.04. Found: C, 53.13; H, 6.06; N, 9.70; Cl, 13.25.

Workup

  1. filtrationThe solid was filtered
  2. washwashed with copious Et2O
  3. customdried in a vacuum oven overnight

Sources & evidence

ORD record
ord-aec2b4879da04affa9a88131950a3814
Source dataset
uspto-grants-2016_01
Patent number
US09227954B2

Reaction notes

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