Triethylamine → HCID 58008960, compound

HRID 2368829Notes

Reaction equation

HRID 2368829 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:19][C:20]3[N:21]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[CH3:38])[C:22](=[O:31])[C:23]4[C:28]([CH:29]=3)=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:30])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([OH:17])[CH:14]=[C:13]([F:18])[CH:12]=3)[C:3]=12.[Al].C(Br)(Br)(Br)Br.[CH2:45]([O:47][P:48]([O-:52])[O:49][CH2:50][CH3:51])[CH3:46].C(N(CC)CC)C>C1COCC1>[P:48]([OH:52])([OH:49])([O:17][C:15]1[CH:14]=[C:13]([F:18])[CH:12]=[C:11]([C:10]2[C:3]3[C:4](=[N:5][CH:6]=[N:7][C:2]=3[NH2:1])[N:8]([CH2:19][C:20]3[N:21]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[CH3:38])[C:22](=[O:31])[C:23]4[C:28]([CH:29]=3)=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:30])[N:9]=2)[CH:16]=1)=[O:47].[P:48]([O:49][CH2:50][CH3:51])([O:47][CH2:45][CH3:46])([O:17][C:15]1[CH:14]=[C:13]([F:18])[CH:12]=[C:11]([C:10]2[C:3]3[C:4](=[N:5][CH:6]=[N:7][C:2]=3[NH2:1])[N:8]([CH2:19][C:20]3[N:21]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[CH3:38])[C:22](=[O:31])[C:23]4[C:28]([CH:29]=3)=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:30])[N:9]=2)[CH:16]=1)=[O:52]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 11205Carbon tetrabromideHCID 3780918DiethylphosphiteHCID 5359268AluminumHCID 58008590HCID 58008590, compound

Product 2

HCID 58008960HCID 58008960, compoundYield 124.5%HCID 58009045HCID 58009045, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

3-((4-Amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one 4301 (250 mg, 0.5 mmol) was dissolved in anhydrous THF (15 mL) in a round bottom flask in dark (covered by aluminum foil) and cooled to 0° C. under an argon atmosphere. CBr4 (498 mg, 1.5 mmol) was added followed by diethylphosphite (129 μL, 1.0 mmol) and triethylamine (417 μL, 1.5 mmol). The resulting mixture was stirred in dark from 0° C. to RT for 16 h. The mixture was then partitioned between ethyl acetate and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with methanol and dichloromethane to afford the desired product, 3-(4-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluorophenyl diethyl phosphate 4302 (200 mg, 62% yield) as an off-white solid.

Workup

  1. customThe mixture was then partitioned between ethyl acetate and brine
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography on silica gel eluting with methanol and dichloromethane

Sources & evidence

ORD record
ord-a259d1752a3146c99f5b32973df121ac
Source dataset
uspto-grants-2014_04
Patent number
US08703777B2

Reaction notes

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