Ammonium Hydroxide → HCID 10479970, compound

HRID 1784983Notes

Reaction equation

HRID 1784983 reaction equation
C1(C(O)=O)CC1.[CH:7]1([C:10]([NH:12][C:13]2[CH:14]=[CH:15][CH:16]=[C:17]3[C:21]=2[C:20](=[O:22])[N:19]([CH:23]([C:28]2[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:37])[F:36])=[C:30]([O:38][CH2:39][CH3:40])[CH:29]=2)[CH2:24][C:25](O)=[O:26])[CH2:18]3)=[O:11])[CH2:9][CH2:8]1.C1N=C[N:43](C(N2C=NC=C2)=O)C=1.[NH4+].[OH-]>C1COCC1>[C:25]([CH2:24][CH:23]([N:19]1[C:20](=[O:22])[C:21]2[C:17](=[CH:16][CH:15]=[CH:14][C:13]=2[NH:12][C:10]([CH:7]2[CH2:9][CH2:8]2)=[O:11])[CH2:18]1)[C:28]1[CH:33]=[CH:32][C:31]([O:34][CH:35]([F:36])[F:37])=[C:30]([O:38][CH2:39][CH3:40])[CH:29]=1)(=[O:26])[NH2:43]

Participants

6

Reactant 4

HCID 14923Ammonium HydroxideHCID 15655Cyclopropanecarboxylic acidHCID 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.; 1H NMR (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, 1H, Ar), 7.46 (t, J=7.5 Hz, 1H, Ar), 8.45 (d, J=8 Hz, 1H, Ar), 10.49 (s, 1H, NHCO). 13C NMR (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-c9af0aea3a2945688050960a30fc418c
Source dataset
uspto-grants-2009_03
Patent number
US07504427B2

Reaction notes

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