Phosphorus oxychloride → 2-chloro-3-iodo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine

HRID 597914Notes

Reaction equation

[I:1][C:2]1[C:19](O)=[N:18][C:5]2[CH2:6][CH2:7][N:8]([C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH2:9][CH:10]([CH3:11])[C:4]=2[CH:3]=1.O=P(Cl)(Cl)[Cl:23]>CN(C=O)C>[Cl:23][C:19]1[C:2]([I:1])=[CH:3][C:4]2[CH:10]([CH3:11])[CH2:9][N:8]([C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])[CH2:7][CH2:6][C:5]=2[N:18]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-iodo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepin-2-ol (137 mg, 342 μmol), DMF (100 μl) and POCl3 (5 ml) was heated at 100° C. for 16 h. The reaction mixture was concentrated in vacuo and purified by column chromatography to furnish 57.0 mg (40%) of 2-chloro-3-iodo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. MS (ESI) m/z 419.1/421.1. A mixture of 2-chloro-3-iodo-5-methyl-7-(trifluoroacetyl)-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine (58.0 mg, 139 μmol), K2CO3 (50 mg) and MeOH (10 ml) was heated for 1 h at 60° C. The reaction mixture was concentrated in vacuo and purified by column chromatography furnishing 37.7 mg (84%) of 2-chloro-3-iodo-5-methyl-6,7,8,9-tetrahydro-5H-pyrido[2,3-d]azepine. 1H-NMR (CDCl3) δ 7.86 (s, 1H), 3.13 (m, 2H), 3.07-2.92 (m, 4H), 2.75 (dd, 1H), 1.33 (d, 3H) ppm.

Workup

concentrationThe reaction mixture was concentrated in vacuo
custompurified by column chromatography

Sources & evidence

ORD record: ord-2f650756891c4023a5df837f3572891e
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07897595B2

Reaction notes

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