(R)-5-(5-amino-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepane-3-thione → 8-(3-((R)-6,6-difluoro-5,7,7-trimethyl-3-thioxo-1,4-oxazepan-5-yl)-4-fluorophenylamino)-5,6,7,8-tetrahydroquinoline-3-carbonitrile

HRID 403247Notes

Reaction equation

HRID 403247 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:21])=[C:6]([C@:8]2([CH3:20])[C:14]([F:16])([F:15])[C:13]([CH3:18])([CH3:17])[O:12][CH2:11][C:10](=[S:19])[NH:9]2)[CH:7]=1.O=[C:23]1[C:32]2[N:31]=[CH:30][C:29]([C:33]#[N:34])=[CH:28][C:27]=2[CH2:26][CH2:25][CH2:24]1>>[F:15][C:14]1([F:16])[C:13]([CH3:17])([CH3:18])[O:12][CH2:11][C:10](=[S:19])[NH:9][C@@:8]1([C:6]1[CH:7]=[C:2]([NH:1][CH:23]2[C:32]3[N:31]=[CH:30][C:29]([C:33]#[N:34])=[CH:28][C:27]=3[CH2:26][CH2:25][CH2:24]2)[CH:3]=[CH:4][C:5]=1[F:21])[CH3:20]

Participants

3

Reactant 2

HCID 58563112(R)-5-(5-amino-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepane-3-thioneHCID 682272435,6,7,8-Tetrahydro-8-oxo-3-quinolinecarbonitrile

Product 1

HCID 866709078-(3-((R)-6,6-difluoro-5,7,7-trimethyl-3-thioxo-1,4-oxazepan-5-yl)-4-fluorophenylamino)-5,6,7,8-tetrahydroquinoline-3-carbonitrileYield 63.2%

Procedure

Prepared in an analogous manner as described for intermediate A22A from (R)-5-(5-amino-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepane-3-thione (intermediate A19B) (102 mg, 320 μmol) and 8-oxo-5,6,7,8-tetrahydroquinoline-3-carbonitrile (66.2 mg, 384 μmol). The 8-(3-((R)-6,6-difluoro-5,7,7-trimethyl-3-thioxo-1,4-oxazepan-5-yl)-4-fluorophenylamino)-5,6,7,8-tetrahydroquinoline-3-carbonitrile (96 mg, 63.1%) was obtained as a white foam. MS (ISN): m/z=473.1 [(M−H)−].

Workup

  1. customPrepared in an analogous manner

Sources & evidence

ORD record
ord-17dd5c0153274e259247ae1490c92b5e
Source dataset
uspto-grants-2014_06
Patent number
US08748418B2

Reaction notes

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