Water → HCID 71285599, compound

HRID 536530Notes

Reaction equation

HRID 536530 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:15]=[C:16](I)[C:17]3[C:22]([CH3:24])([CH3:23])[C:21](=[O:25])[NH:20][C:18]=3[N:19]=2)=[N:6]1.C(N(CC)C(C)C)(C)C.Cl.Cl.[NH:42]1[CH2:45][CH:44]([N:46]2[CH2:50][CH2:49][CH2:48][CH2:47]2)[CH2:43]1.O>CN1CCCC1=O>[F:1][C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][CH:11]=[CH:12][CH:13]=[C:8]2[C:7]([C:14]2[N:15]=[C:16]([N:42]3[CH2:45][CH:44]([N:46]4[CH2:50][CH2:49][CH2:48][CH2:47]4)[CH2:43]3)[C:17]3[C:22]([CH3:24])([CH3:23])[C:21](=[O:25])[NH:20][C:18]=3[N:19]=2)=[N:6]1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 19423677Pyrrolidine, 1-(3-azetidinyl)-, dihydrochlorideHCID 867053672-[1-(2-Fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-iodo-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

Product 1

HCID 71285599HCID 71285599, compoundYield 48.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

150 mg (0.21 mmol, purity approx. 71%) of 2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-iodo-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (example 15A) was dissolved in 1-methyl-2-pyrrolidone (3.1 ml) in a reaction vessel suitable for a microwave, and 0.29 ml (1.66 mmol) of N,N-diisopropyl ethylamine and 165 mg (0.83 mmol) of 1-(azetidin-3-yl)pyrrolidine-dihydrochloride were added. Then the reaction vessel was sealed with a septum and heated in the microwave at 150° C. for 6 h. After cooling, water was added to the reaction mixture. It was stirred for 30 min and filtered to remove the resultant solid. The filtrate was purified by preparative HPLC (acetonitrile:water (+0.1% trifluoroacetic acid) gradient). The product fraction was dissolved in dichloromethane and was washed twice with saturated aqueous sodium hydrogen carbonate solution. The organic phase was dried over sodium sulphate, filtered and concentrated by evaporation. 52 mg of the title compound was obtained (46% of theor.; purity 94%).

Workup

  1. additionwere added
  2. customThen the reaction vessel was sealed with a septum
  3. temperatureAfter cooling
  4. filtrationfiltered
  5. customto remove the resultant solid
  6. customThe filtrate was purified by preparative HPLC (acetonitrile:water (+0.1% trifluoroacetic acid) gradient)
  7. dissolutionThe product fraction was dissolved in dichloromethane
  8. washwas washed twice with saturated aqueous sodium hydrogen carbonate solution
  9. dry with materialThe organic phase was dried over sodium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-fe19484c0e6d4d9198975c40a560dce6
Source dataset
uspto-grants-2014_10
Patent number
US08859569B2

Reaction notes

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