Hydrogen Bromide → 5-bromo-2-(2,5-dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide

HRID 1687781Notes

Reaction equation

HRID 1687781 reaction equation
[NH2:1][C:2]1[C:11]([F:12])=[CH:10][C:9]([Br:13])=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5].Br.CN1CCCC1=O.C(N(CC)C(C)C)(C)C.[Cl:31][C:32]1[N:37]=[C:36](Cl)[C:35]([Cl:39])=[CH:34][N:33]=1>>[Br:13][C:9]1[CH:10]=[C:11]([F:12])[C:2]([NH:1][C:34]2[C:35]([Cl:39])=[CH:36][N:37]=[C:32]([Cl:31])[N:33]=2)=[C:3]([CH:8]=1)[C:4]([NH:6][CH3:7])=[O:5]

Participants

6

Reactant 5

HCID 260Hydrogen BromideHCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 2372592,4,5-TrichloropyrimidineHCID 672637462-Amino-5-bromo-3-fluoro-N-methyl-benzamide

Product 1

HCID 866340355-bromo-2-(2,5-dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamideYield 50%

Conditions

Temperature
100 °C

Procedure

2-Amino-5-bromo-3-fluoro-N-methyl-benzamide; hydrobromide (2.00 g, 6.10 mmol) was placed in N-methylpyrrolidinone (20.0 mL, 207 mmol) and N,N-diisopropylethylamine (3.19 mL, 18.3 mmol) was added. The reaction was stirred for 5 minutes and then 2,4,5-trichloro-pyrimidine (3.50 mL, 30.5 mmol) was added. The reaction was heated at 100° C. for 24 hours and then concentrated under reduced pressure. The residue was taken up in DCM (100 mL) and washed twice with water (100 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. Purification by silica gel chromatography using a gradient of 0-40% EtOAc/hex as the eluting solvent to obtain 5-bromo-2-(2,5-dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide as a tan solid (1.19 g, 50%). m.p.=246-249° C.; LCMS (m/e) 393 (M+H); 1H-NMR (d6-DMSO, 400 MHz) δ 9.73 (s, 1H), 8.68-8.57 (m, 1H), 8.43 (s, 1H), 7.87 (d, 1H, J=9.6 Hz), 7.66 (s, 1H), 2.69 (d, 3H, J=3.9 Hz); 19F-NMR (d6-DMSO, 400 MHz)6-113.

Workup

  1. concentrationconcentrated under reduced pressure
  2. washwashed twice with water (100 mL)
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customPurification by silica gel chromatography

Sources & evidence

ORD record
ord-2a183b8280394f7c9a4dcee071661cdf
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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