2-[5-chloro-2-(5-methyl-6-oxo-5,6,8,9-tetrahydro-7-oxa-5-aza-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-3-fluoro-N-prop-2-ynyl-benzamide → 2-{5-chloro-4-[2-fluoro-6-(5-methylene-4,5-dihydro-oxazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one

HRID 1041757Notes

Reaction equation

HRID 1041757 reaction equation
[Cl:1][C:2]1[C:3]([NH:22][C:23]2[C:34]([F:35])=[CH:33][CH:32]=[CH:31][C:24]=2[C:25]([NH:27][CH2:28][C:29]#[CH:30])=[O:26])=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[N:18]([CH3:19])[C:17](=[O:20])[O:16][CH2:15][CH2:14][C:13]=3[CH:21]=2)=[N:6][CH:7]=1>C(#N)C.[Au](Cl)(Cl)Cl>[Cl:1][C:2]1[C:3]([NH:22][C:23]2[C:24]([C:25]3[O:26][C:29](=[CH2:30])[CH2:28][N:27]=3)=[CH:31][CH:32]=[CH:33][C:34]=2[F:35])=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]3[N:18]([CH3:19])[C:17](=[O:20])[O:16][CH2:15][CH2:14][C:13]=3[CH:21]=2)=[N:6][CH:7]=1

Participants

4

Reactant 1

HCID 866340832-[5-chloro-2-(5-methyl-6-oxo-5,6,8,9-tetrahydro-7-oxa-5-aza-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-3-fluoro-N-prop-2-ynyl-benzamide

Product 1

HCID 672639032-{5-chloro-4-[2-fluoro-6-(5-methylene-4,5-dihydro-oxazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-oneYield 74.1%

Reagents, catalysts & solvents 2

HCID 26030Gold trichlorideCatalystHCID 6342AcetonitrileSolvent

Procedure

A suspension of 2-[5-chloro-2-(5-methyl-6-oxo-5,6,8,9-tetrahydro-7-oxa-5-aza-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-3-fluoro-N-prop-2-ynyl-benzamide (108 mg) and gold (III) chloride (20 mg) in acetonitrile (20 mL) was stirred for 16 hours and filtered. The filtrate was concentrated and purified by silica gel chromatography to provide 2-{5-chloro-4-[2-fluoro-6-(5-methylene-4,5-dihydro-oxazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one (80 mg): 1H NMR (300 MHz, CDCl3) δ 10.10 (bs, 1H), 8.20 (s, 1H), 7.84 (dd, 1H), 7.46-7.34 (m, 4H), 7.14 (bs, 1H), 7.06 (d, 1H), 4.96 (dd, 1H), 4.82 (t, 1H), 4.56-4.50 (m, 2H), 3.45 (s, 3H), 2.92 (t, 1H).

Workup

  1. filtrationfiltered
  2. concentrationThe filtrate was concentrated
  3. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-ffac6f585c104c2b8a3a90d0ee0853a9
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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