Pyridine → 3-[(1S,2S)-2-((3R,6R)-6-Cyclohexylmethoxymorpholin-3-yl)-1-(3,5-difluorobenzyl)-2-hydroxyethyl]-1-hexyl-1-methylurea hydrochloride

HRID 20481Notes

Reaction equation

[CH2:1]([N:7]([CH3:11])[C:8]([Cl:10])=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(OC([N:19]1[C@@H:24]([C@@H:25]([OH:37])[C@@H:26]([NH2:36])[CH2:27][C:28]2[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[CH:29]=2)[CH2:23][O:22][C@@H:21]([O:38][CH2:39][CH:40]2[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]2)[CH2:20]1)=O)(C)(C)C.N1C=CC=CC=1>ClCCl>[ClH:10].[CH:40]1([CH2:39][O:38][C@H:21]2[CH2:20][NH:19][C@@H:24]([C@@H:25]([OH:37])[C@@H:26]([NH:36][C:8](=[O:9])[N:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH3:11])[CH2:27][C:28]3[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[CH:29]=3)[CH2:23][O:22]2)[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1

Participants

Conditions

Temperature: 55 °C

Procedure

Add hexylmethylcarbamic chloride (11 mg, 0.062 mmol) to a solution of (2R,5R)-5-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2-cyclohexylmethoxymorpholine-4-carboxylic acid tert-butyl ester (30 mg, 0.062 mmol) and pyridine (10 μL, 0.123 mmol) in dichloromethane at 0° C. Heat to 55° C. for four days. Perform purification, isolation, trifluoroacetic acid deprotection and salt exchange according to the procedure essentially as described for (E)-2-methyl-but-2-enoic acid [(1S,2S)-2-((3R,6R)-6-cyclohexylmethoxymorpholin-3-yl)-1-(3,5-difluorobenzyl)-2-hydroxyethyl]-amide hydrochloride.

Workup

customPerform purification, isolation, trifluoroacetic acid deprotection and salt exchange

Sources & evidence

ORD record: ord-d475f1371dc8473ba0800be32dd3b36d
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745438B2

Reaction notes

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