Potassium Phosphate, Tribasic → HCID 25156756, compound

HRID 1041740Notes

Reaction equation

HRID 1041740 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[S:6][C:7](Br)=[C:8]([CH3:32])[C:9]=1[NH:10][C:11]1[C:16]([Cl:17])=[CH:15][N:14]=[C:13]([NH:18][C:19]2[CH:20]=[CH:21][C:22]3[N:28]([CH3:29])[C:27](=[O:30])[O:26][CH2:25][CH2:24][C:23]=3[CH:31]=2)[N:12]=1)=[O:4].[CH3:34]B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][NH:2][C:3]([C:5]1[S:6][C:7]([CH3:34])=[C:8]([CH3:32])[C:9]=1[NH:10][C:11]1[C:16]([Cl:17])=[CH:15][N:14]=[C:13]([NH:18][C:19]2[CH:20]=[CH:21][C:22]3[N:28]([CH3:29])[C:27](=[O:30])[O:26][CH2:25][CH2:24][C:23]=3[CH:31]=2)[N:12]=1)=[O:4]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 139377Methylboronic AcidHCID 66829676HCID 66829676, compound

Product 1

HCID 25156756HCID 25156756, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-bromo-3-[5-chloro-2-(5-methyl-6-oxo-5,6,8,9-tetrahydro-7-oxa-5-aza-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-4-methyl-thiophene-2-carboxylic acid methylamide (50 mg, 0.09 mmol), methylboronic acid (16.4 mg, 0.27 mmol), 2 M aqueous potassium phosphate solution (2 mL) and tetrakis(triphenylphosphine)palladium(0) (6 mg, 0.004 mmol) in 1,4-dioxane (2 mL) was heated at 100° C. for 24 hours. The mixture was cooled and extracted with methylene chloride. The organic layer was washed with brine, dried over by sodium sulfate, and concentrated. Chromatography with preparative TLC (methylene chloride and methanol (40:1)) followed by semipreparative HPLC gave of 5-methyl-3-[5-chloro-2-(5-methyl-6-oxo-5,6,8,9-tetrahydro-7-oxa-5-aza-benzocyclohepten-2-ylamino)-pyrimidin-4-ylamino]-4-methyl-thiophene-2-carboxylic acid methylamide (2 mg, 5%): 1H NMR (300 MHz, CDCl3) δ 8.1 (s, 1H), 7.44 (d, 1H), 7.33 (d, 1H), 7.0 (d, 1H), 6.53 (q, 1H), 4.48 (t, 2H), 3.38 (s, 3H), 2.94 (d, 3H), 2.83 (t, 2H), 2.43 (s, 3H), 1.95 (s, 3H); MS (m/e): 487.3 (M+1).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with methylene chloride
  3. washThe organic layer was washed with brine
  4. dry with materialdried over by sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-08ae95c6e2ae4d179cd14a4bb1478f4a
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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