Ammonium Hydroxide → 3-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionamide

HRID 1784986Notes

Reaction equation

HRID 1784986 reaction equation
[C:1]([NH:4][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:13]=1[C:12](=[O:14])[N:11]([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]([OH:19])=O)[CH2:10]2)(=[O:3])[CH3:2].C1N=C[N:35](C(N2C=NC=C2)=O)C=1.[NH4+].[OH-]>C1COCC1>[C:1]([NH:4][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:13]=1[C:12](=[O:14])[N:11]([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]([NH2:35])=[O:19])[CH2:10]2)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 104788263-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid

Product 1

HCID 99810493-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionamideYield 73.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-(7-Acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionamide was prepared by the procedure of example 6 from 3-[7-(acetylamino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid (0.6 g, 1.3 mmol), CDI (0.3 g, 2 mmol) and NH4OH (0.20 ml, 2.6 mmol) in THF (30 ml) to give 3-(7-acetylamino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionamide as white solid (0.43 g, 72%): mp 129-131° C.; 1H NMR (CDCl3): δ 1.44 (t, J=7.0 Hz, 3H, OCH2CH3), 2.25 (s, 3H, CH3CO), 2.97 (dd, J=5, 15 Hz, 1H, CH2), 3.42 (dd, J=10, 15 Hz, 1H, CH2), 4.08 (q, J=7.0 Hz, 2H, OCH2CH3), 4.20 (d, J=17.5 Hz, 1H, CH2N), 4.40 (d, J=17.5 Hz, 1H, CH2N), 5.40 (broad, 1H, NH2), 5.56 (m, 1H, CHN), 6.01 (broad, 1H), 6.56 (t, JH-F=75 Hz, 1H, CF2H), 6.95 (m, 3H, Ar), 7.15 (d, J=7.5 Hz, 1H, Ar), 7.47 (t, J=7.5 Hz, 1H, Ar), 8.47 (d, J=7.5 Hz, 1H, Ar), 10.25 (s, 1H, NHCO). 13C NMR (DMSO-d6): δ 3.2, 14.4, 16.2, 24.4, 37.7, 46.7, 51.7, 64.2, 93.9, 113.0, 116.6, 117.2, 117.5, 119.2, 121.3, 132.8, 137.0, 138.2, 139.0, 142.2, 149.8, 168.0, 168.5, 171.0; Anal. Calcd. for C22H23F2N3O5: C, 59.06; H, 5.18; N, 9.39; Found: C, 58.48; H, 5.12; N, 9.65.

Sources & evidence

ORD record
ord-a1cb7d322d184b009605a104f89bc80b
Source dataset
uspto-grants-2009_03
Patent number
US07504427B2

Reaction notes

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