Hydrochloric Acid → HCID 46198729, compound

HRID 588036Notes

Reaction equation

HRID 588036 reaction equation
[Si]([O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][CH2:19][C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[C:25](=[O:29])[N:24]([CH:30]2[CH2:35][CH2:34][C:33](=[O:36])[NH:32][C:31]2=[O:37])[CH2:23]3)=[O:17])=[CH:11][C:10]=1[CH3:38])(C(C)(C)C)(C)C.Cl>C(Cl)Cl.CCOCC>[O:37]=[C:31]1[CH:30]([N:24]2[CH2:23][C:22]3[C:26](=[CH:27][CH:28]=[C:20]([CH2:19][NH:18][C:16]([NH:15][C:12]4[CH:13]=[CH:14][C:9]([OH:8])=[C:10]([CH3:38])[CH:11]=4)=[O:17])[CH:21]=3)[C:25]2=[O:29])[CH2:35][CH2:34][C:33](=[O:36])[NH:32]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 66589535HCID 66589535, compound

Product 1

HCID 46198729HCID 46198729, compoundYield 105.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Step 3 (0.5 g, 0.9 mmol) in methylene chloride (20 mL) was added 2N HCl in ether (2 mL). The mixture stirred for 16 h at ambient temperature. The precipitated product was isolated by filtration, and was rinsed with methylene chloride (20 mL) and dried under vacuum, providing 0.4 g of 1-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-3-(4-hydroxy-3-methylphenyl)urea as an off-white solid, in quantitative yield; HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 ml/min, 240 nm, 30/70 CH3CN/0.1% H3PO4, 1.88 min (96.94%); mp 210-212 0C; 1H NMR (DMSO-d6) δ 1.94-2.18 (m, 4H), 2.30-2.51 (m, 1H), 2.58-2.72 (m, 1H), 2.87-3.06 (m, 1H), 4.25-4.56 (m, 4H), 5.15 (dd, J=5.0, 13.3 Hz, 1H), 6.67 (d, J=8.5 Hz, 1H), 7.02 (dd, J=2.5, 8.6 Hz, 1H), 7.12 (d, J=2.3 Hz, 1H), 7.47 (d, J=7.7 Hz, 1H), 7.54 (s, 1H), 7.73 (d, J=7.7 Hz, 1H), 8.32 (br. s., 1H), 11.02 (s, 1H); 13C NMR (DMSO-d6) δ 16.15, 22.51, 31.20, 42.77, 47.12, 51.56, 114.47, 117.11, 121.32, 121.83, 122.88, 123.61, 126.86, 130.22, 131.72, 142.35, 145.17, 150.10, 155.58, 170.99, 172.85; LCMS MH=423; Anal. Calcd for C22H22N4O5+0.25CH2Cl2: C, 60.23; H, 5.11; N, 12.63. Found: C, 60.14; H, 5.43; N, 12.54.

Workup

  1. customThe precipitated product was isolated by filtration
  2. washwas rinsed with methylene chloride (20 mL)
  3. customdried under vacuum

Sources & evidence

ORD record
ord-706955f418c740999c34e08c7fc4ea51
Source dataset
uspto-grants-2016_01
Patent number
US09227954B2

Reaction notes

Loading…