Ammonium Hydroxide → HCID 10391526, compound

HRID 346911Notes

Reaction equation

HRID 346911 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([CH:14]2[CH2:16][CH2:15]2)=[O:13])=[C:7]2[C:3]=1[CH2:4][N:5]([CH:18]([C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:32])[F:31])=[C:25]([O:33][CH2:34][CH3:35])[CH:24]=1)[CH2:19][C:20]([OH:22])=O)[C:6]2=[O:17].C1N=C[N:38](C(N2C=NC=C2)=O)C=1.[NH4+].[OH-]>C1COCC1>[C:20]([CH2:19][CH:18]([N:5]1[C:6](=[O:17])[C:7]2[C:3](=[C:2]([Cl:1])[CH:10]=[CH:9][C:8]=2[NH:11][C:12]([CH:14]2[CH2:15][CH2:16]2)=[O:13])[CH2:4]1)[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH:30]([F:31])[F:32])=[C:25]([O:33][CH2:34][CH3:35])[CH:24]=1)(=[O:22])[NH2:38]

Participants

5

Reactant 3

HCID 14923Ammonium HydroxideHCID 682631,1'-CarbonyldiimidazoleHCID 21082335HCID 21082335, compound

Product 1

HCID 10391526HCID 10391526, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Cyclopropanecarboxylic acid {2-[2-carbamoyl-1-(4-difluoromethoxy-3-ethoxy-phenyl)-ethyl]-7-chloro-3-oxo-2,3-dihydro-1H-isoindol-4-yl }-amide was prepared by the procedure of Example 6 from 3-[4-chloro-7-(cyclopropanecarbonylamino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(4-difluoromethoxy-3-ethoxy-phenyl)-propionic acid (0.55 g, 1.1 mmol), CDI (0.26 g, 1.6 mmol) and NH4OH (0.35 ml, 3.3 mmol) in THF (15 ml) to give cyclopropanecarboxylic acid {2-[2-carbamoyl-1-(4-difluoromethoxy-3-ethoxy-phenyl)-ethyl]-7-chloro-3-oxo-2,3-dihydro-1H-isoindol-4-yl}-amide as white solid (0.10 g, 20%): mp 198–200° C.; 1HNMR (CDCl3): δ 0.89–0.93 (m, 2H, c-CH2), 1.10–1.20 (m, 2H, c-CH2), 1.44 (t, J=7.5 Hz, 3H, OCH2CH3), 1.66–1.68 (m, 1H, c-CH), 2.98 (dd, J=5, 15 Hz, 1H, CH2), 3.43 (dd, J=10, 15 Hz, 1H, CH2), 4.09 (q, J=7.5 Hz, 2H, OCH2CH3), 4.18 (d, J=17.5 Hz, 1H, CHHN), 4.37 (d, J=17.5 Hz, 1H, CHHN), 5.48 (br, 1H, NHH), 5.57–5.53 (m, 1H, CHN), 5.92 (br, 1H, NHH), 6.86 (t, JH-F=75 Hz, 1H, CF2H), 6.94–7.02 (m, 3H, Ar), 7.16(d, J=10 Hz, 1H, Ar), 7.38 (t, J=8 Hz, 1H, Ar), 8.45 (d, J=8 Hz, 1H, Ar), 10.40 (s, 1H, NHCO). 13CNMR (CDCl3): δ 8.5, 14.6, 16.2, 38.6, 47.9, 54.1, 64.9, 101.57, 102.3, 113.2, 116.0, 119.2, 119.8, 121.8, 123.0, 133.2, 136.8, 137.1, 139.1, 150.9, 169.4, 171.1, 172.6; Anal Calcd for C24H26ClF2N3O5: C, 56.75; H, 4.76; N, 8.27. Found: C, 56.68; H, 4.63; N, 8.04.

Sources & evidence

ORD record
ord-62f61f871ac04f8babdb9d59bf7ee0eb
Source dataset
uspto-grants-2007_02
Patent number
US07173058B2

Reaction notes

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