Ammonium Hydroxide → HCID 10479970, compound

HRID 1367077Notes

Reaction equation

HRID 1367077 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[CH:8]=[CH:9][CH:10]=[C:11]3[C:15]=2[C:14](=[O:16])[N:13]([CH:17]([C:22]2[CH:27]=[CH:26][C:25]([O:28][CH:29]([F:31])[F:30])=[C:24]([O:32][CH2:33][CH3:34])[CH:23]=2)[CH2:18][C:19](O)=[O:20])[CH2:12]3)=[O:5])[CH2:3][CH2:2]1.C1N=C[N:37](C(N2C=NC=C2)=O)C=1.[NH4+].[OH-]>C1COCC1>[C:19]([CH2:18][CH:17]([N:13]1[C:14](=[O:16])[C:15]2[C:11](=[CH:10][CH:9]=[CH:8][C:7]=2[NH:6][C:4]([CH:1]2[CH2:3][CH2:2]2)=[O:5])[CH2:12]1)[C:22]1[CH:27]=[CH:26][C:25]([O:28][CH:29]([F:30])[F:31])=[C:24]([O:32][CH2:33][CH3:34])[CH:23]=1)(=[O:20])[NH2:37]

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 10027851HCID 10027851, compound

Product 1

HCID 10479970HCID 10479970, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Cyclopropanecarboxylic acid {2-[2-carbamoyl-1-(4-difluoromethoxy-3-ethoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide was prepared by the procedure of example 6 from 3-[7-(cyclopropanecarbonyl-amino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid (0.8 g, 1.7 mmol), CDI (0.41 g, 2.5 mmol) and NH4OH (0.25 ml, 3.4 mmol) in THF (30 ml) to give cyclopropanecarboxylic acid {2-[2-carbamoyl-1-(4-difluoromethoxy-3-ethoxy-phenyl)-ethyl]-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (0.56 g, 70%): mp, 179-181° C.; 1HNMR (CDCl3): δ 0.92 (m, 2H, c-CH2), 1.44 (t, J=6.8 Hz, 3H, OCH2CH3), 1.68 (m, 1H, c-CH), 2.99 (dd, J=5, 15 Hz, 1H, CH2), 3.44 (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), 5.42 (broad, 1H, NH2), 5.58 (m, 1H, CHN), 6.07 (broad, 1H), 6.56 (t, JH-F=75 Hz, 1H, CF2H), 6.98 (m, 3H, Ar), 7.15 (d, J=7.5 Hz, H, Ar), 7.46 (t, J=7.5 Hz, 1H, Ar), 8.45 (d, J=8 Hz, 1H, Ar), 10.49 (s, 1H, NHCO). 13CNMR (CDCl3): δ 8.31, 14.6, 16.2, 38.9, 48.6, 53.9, 64.8, 101.57, 102.3, 113.2, 116.7, 117.3, 117.8, 119.2, 122.9, 113.5, 137.3, 138.1, 141.4, 141.2, 150.9, 170.9, 171.4, 172.7; Anal. Calcd. for C24H25F2N3O5: C, 60.88; H, 5.32; N, 8.87. Found: C, 60.82; H, 5.11; N, 8.80.

Sources & evidence

ORD record
ord-d98f3d14e9f7497399a5a65a71bea540
Source dataset
uspto-grants-2011_02
Patent number
US07893102B2

Reaction notes

Loading…