Water → HCID 71290302, compound

HRID 536495Notes

Reaction equation

HRID 536495 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.[C:40]([O:44][C:45](=[O:51])[NH:46][CH:47]1[CH2:50][NH:49][CH2:48]1)([CH3:43])([CH3:42])[CH3:41].O>CN1CCCC1=O>[C:40]([O:44][C:45](=[O:51])[NH:46][CH:47]1[CH2:50][N:49]([C:16]2[C:17]3[C:22]([CH3:24])([CH3:23])[C:21](=[O:25])[NH:20][C:18]=3[N:19]=[C:14]([C:7]3[C:8]4[C:9](=[N:10][CH:11]=[CH:12][CH:13]=4)[N:5]([CH2:4][C:3]4[CH:27]=[CH:28][CH:29]=[CH:30][C:2]=4[F:1])[N:6]=3)[N:15]=2)[CH2:48]1)([CH3:43])([CH3:41])[CH3:42]

Participants

6

Reactant 4

HCID 962WaterHCID 81531Diisopropylethylamine2×HCID 15194053-Aminoazetidine, 3-BOC protected2×HCID 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 71290302HCID 71290302, compoundYield 69%

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 a reaction vessel suitable for a microwave, in 1-methyl-2-pyrrolidone (3.1 ml), and 0.22 ml (1.24 mmol) of N,N-diisopropyl ethylamine and 143 mg (0.83 mmol) of tert.-butyl-azetidin-3-ylcarbamate were added. Then the reaction vessel was sealed with a septum and heated for 8 h at 150° C. in the microwave. Then 0.15 ml (0.82 mmol) of N,N-diisopropyl ethylamine and 107 mg (0.62 mmol) of tert.-butyl-azetidin-3-ylcarbamate were added again and the reaction mixture was heated for 3 h at 150° C. in the microwave. After cooling, water was added to the reaction mixture and it was purified by preparative HPLC (acetonitrile:water (+0.1% trifluoroacetic acid) gradient). 81 mg of the title compound was obtained (64% of theor.; purity 91%).

Workup

  1. customThen the reaction vessel was sealed with a septum
  2. temperaturethe reaction mixture was heated for 3 h at 150° C. in the microwave
  3. temperatureAfter cooling
  4. customwas purified by preparative HPLC (acetonitrile:water (+0.1% trifluoroacetic acid) gradient)

Sources & evidence

ORD record
ord-115b0a33f145489baca5f3d06cef9fb2
Source dataset
uspto-grants-2014_10
Patent number
US08859569B2

Reaction notes

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