Dimethylamine → 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-N,N-dimethyl-propionamide

HRID 346906Notes

Reaction equation

HRID 346906 reaction equation
[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:33])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:29])[F:28])=[C:22]([O:30][CH2:31][CH3:32])[CH:21]=1)[CH2:16][C:17](O)=[O:18])[C:9]2=[O:14])(=[O:3])[CH3:2].C1N=[CH:37][N:36](C(N2C=NC=C2)=O)[CH:35]=1.CNC>C1COCC1>[C:1]([NH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[C:7](=[O:33])[N:8]([CH:15]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH:27]([F:28])[F:29])=[C:22]([O:30][CH2:31][CH3:32])[CH:21]=1)[CH2:16][C:17]([N:36]([CH3:37])[CH3:35])=[O:18])[C:9]2=[O:14])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 674DimethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 10411999HCID 10411999, compound

Product 1

HCID 100284843-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-N,N-dimethyl-propionamideYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-(4-Acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-N,N-dimethyl-propionamide was prepared by the procedure of example 13 from 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid (0.5 g, 1.1 mmol), CDI (0.2 g, 0.1.3 mmol) and dimethylamine (2N in THF, 0.7 ml, 1.4 mmol) in THF (10 ml) to give 3-(4-acetylamino-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy -phenyl)-N,N-dimethyl-propionamide (0.35 g, 67% yield): mp,163–165° C.; 1HNMR (CDCl3): δ1.44 (t, J=7.0 Hz, 3H, OCH2CH3), 2.25 (s, 3H, CH3CO), 2.90 (s, 3H, NCH3), 2.98 (dd, J=5, 15 Hz, 1H, CH2), 3.05 (s, 4H, NCH3+CH2), 3.91 (dd, J=10, 15 Hz, 1H, CH2), 4.09 (q, J=7.0 Hz, 2H, OCH2CH3), 5.81–5.87 (m, 1H, CHN), 6.53 (t, JH-F=75 Hz, 1H, CF2H), 7.11–7.17 (m, 3H, Ar), 7.45 (d, J=7.0 Hz, 1H, Ar), 7.62 (t, J=8.0 Hz, 1H, Ar), 8.73(d, J=8.8 Hz, 1H, Ar), 9.53 (s, 1H, NHCO). 13CNMR (DMSO-d6): δ 14.5, 24.8, 34.8, 35.5, 37.1, 51.3, 64.7, 111.9, 113.8, 115.4, 116.1, 117.9, 120.1, 120.2, 122.7, 124.7, 131.3, 135.8, 137.5, 138.1, 150.6, 168.1, 169.2, 169.3, 170.0; Anal Calcd for C24H25F2N3O6: C, 58.89; H, 5.15; N, 8.58. Found: C, 58.53; H, 4.78; N, 8.51.

Sources & evidence

ORD record
ord-a6cfc4120ed548b3b092499ca27307fd
Source dataset
uspto-grants-2007_02
Patent number
US07173058B2

Reaction notes

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