1-Bromo-2-Chloroethane → 5-[3-({1-[2-(2-Chloroethoxy)phenyl]cyclopropyl}amino)-2-oxopyrazin-1(2H)-yl]-N-cyclopropyl-2-fluoro-4-methylbenzamide

HRID 1697401Notes

Reaction equation

[CH:1]1([NH:4][C:5](=[O:32])[C:6]2[CH:11]=[C:10]([N:12]3[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]4([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=5[OH:28])[CH2:21][CH2:20]4)[C:13]3=[O:29])[C:9]([CH3:30])=[CH:8][C:7]=2[F:31])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:40][CH2:41][Cl:42]>C(#N)C>[Cl:42][CH2:41][CH2:40][O:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:19]1([NH:18][C:14]2[C:13](=[O:29])[N:12]([C:10]3[C:9]([CH3:30])=[CH:8][C:7]([F:31])=[C:6]([CH:11]=3)[C:5]([NH:4][CH:1]3[CH2:2][CH2:3]3)=[O:32])[CH:17]=[CH:16][N:15]=2)[CH2:21][CH2:20]1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of N-cyclopropyl-2-fluoro-5-[3-{[1-(2-hydroxyphenyl)cyclopropyl]amino}-2-oxopyrazin-1(2H)-yl]-4-methylbenzamide (Example 318g, 1.189 g) in acetonitrile (30 mL) was added potassium carbonate (3.78 g) followed by 1-bromo-2-chloroethane (4.54 mL). The reaction was heated at 95° C. for 32 h under nitrogen. The reaction was cooled to room temperature, filtered through celite, and the cake washed with further acetonitrile. The filtrate was collected and the solvents removed in vacuo to give the subtitle compound (1.368 g).

Workup

temperatureThe reaction was cooled to room temperature
filtrationfiltered through celite
washthe cake washed with further acetonitrile
customThe filtrate was collected
customthe solvents removed in vacuo

Sources & evidence

ORD record: ord-85ae96d523c74892a83fe7cacbc7e8f7
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163905B2

Reaction notes

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