1,4-Dioxane hydrochloride → 2-{5-chloro-4-[2-fluoro-6-(5-methyl-oxazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one

HRID 1041758Notes

Reaction equation

HRID 1041758 reaction equation
[Cl:1][C:2]1[C:3]([NH:22][C:23]2[C:28]([C:29]3[O:30][C:31](=[CH2:34])[CH2:32][N:33]=3)=[CH:27][CH:26]=[CH:25][C:24]=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.Cl.O1CCOCC1>C(#N)C>[Cl:1][C:2]1[C:3]([NH:22][C:23]2[C:28]([C:29]3[O:30][C:31]([CH3:34])=[CH:32][N:33]=3)=[CH:27][CH:26]=[CH:25][C:24]=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 2

HCID 204431481,4-Dioxane hydrochlorideHCID 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-one

Product 1

HCID 251559172-{5-chloro-4-[2-fluoro-6-(5-methyl-oxazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-oneYield 82.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 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) in acetonitrile (10 mL) was added 4N HCl/dioxane (0.3 mL). The mixture was stirred for 16 hours, concentrated, and triturated with ethyl ether to provide 66 mg of 2-{5-chloro-4-[2-fluoro-6-(5-methyl-oxazol-2-yl)-phenylamino]-pyrimidin-2-ylamino}-5-methyl-8,9-dihydro-5H-7-oxa-5-aza-benzocyclohepten-6-one as an HCl salt: 1H NMR (300 MHz, CD3OD) δ 8.22 (s, 1H), 7.94 (d, 1H), 7.58 (dd, 1H), 7.42 (t, 1H), 7.22-7.10 (m, 3H), 7.95 (s, 1H), 4.40 (t, 2H), 3.35 (s, 3H), 2.85 (t, 2H), 2.40 (s, 3H); MS (m/e) 495 (M+1).

Workup

  1. concentrationconcentrated
  2. customtriturated with ethyl ether

Sources & evidence

ORD record
ord-68868a2dea564ee29e82f59a9dc87767
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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