Diisopropylethylamine → 2-[5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-(3-hydroxyazetidin-1-yl)-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

HRID 536529Notes

Reaction equation

HRID 536529 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:12]=[C:13](I)[C:14]4[C:19]([CH3:21])([CH3:20])[C:18](=[O:22])[NH:17][C:15]=4[N:16]=3)=[N:9][N:8]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])[C:5]2=[N:6][CH:7]=1.C(N(CC)C(C)C)(C)C.Cl.[NH:42]1[CH2:45][CH:44]([OH:46])[CH2:43]1.O.FC(F)(F)C(O)=O>CN1CCCC1=O>[F:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:12]=[C:13]([N:42]4[CH2:45][CH:44]([OH:46])[CH2:43]4)[C:14]4[C:19]([CH3:21])([CH3:20])[C:18](=[O:22])[NH:17][C:15]=4[N:16]=3)=[N:9][N:8]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[F:31])[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 22392675Trifluoroacetic acid waterHCID 867053662-[5-Fluoro-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 712858392-[5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-4-(3-hydroxyazetidin-1-yl)-5,5-dimethyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-oneYield 22.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

100 mg (0.18 mmol, approx. 95% purity) of 2-[5-fluoro-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 16A) was dissolved in 1-methyl-2-pyrrolidone (3.1 ml) in a reaction vessel suitable for a microwave, and 0.19 ml (1.07 mmol) of N,N-diisopropyl ethylamine and 97 mg (0.89 mmol) of azetidin-3-ol hydrochloride were added. Then the reaction vessel was sealed with a septum and was heated in the microwave at 150° C. for 3 h. After cooling, water/trifluoroacetic acid was added to the reaction mixture and the resultant solid was filtered off. The filtrate was purified by preparative HPLC (acetonitrile:water (+0.1% trifluoroacetic acid) gradient). 19 mg of the title compound was obtained (21% of theor.; purity 93%).

Workup

  1. additionwere added
  2. customThen the reaction vessel was sealed with a septum
  3. temperatureAfter cooling
  4. filtrationthe resultant solid was filtered off
  5. customThe filtrate was purified by preparative HPLC (acetonitrile:water (+0.1% trifluoroacetic acid) gradient)

Sources & evidence

ORD record
ord-b44c7845157448c99d00d3338f6f499a
Source dataset
uspto-grants-2014_10
Patent number
US08859569B2

Reaction notes

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