Potassium Carbonate → N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-3-({methyl[(3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]amino}sulfonyl)benzamide

HRID 564649Notes

Reaction equation

HRID 564649 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][N:9]([CH3:43])[S:10]([C:13]2[CH:14]=[C:15]([CH:40]=[CH:41][CH:42]=2)[C:16]([NH:18][CH2:19][C:20]2[C:21]([NH:33][CH:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[C:22]3[CH:30]=[N:29][N:28]([CH2:31][CH3:32])[C:23]3=[N:24][C:25]=2[CH2:26][CH3:27])=[O:17])(=[O:12])=[O:11])[CH:5]=[CH:6][CH:7]=1.CC(OC([N:51]1[CH2:56][CH2:55][N:54]([CH2:57][C:58]2[CH:59]=[C:60](B(O)O)[CH:61]=[CH:62][CH:63]=2)[CH2:53][C@H:52]1[CH3:67])=O)(C)C.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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>[CH2:31]([N:28]1[C:23]2=[N:24][C:25]([CH2:26][CH3:27])=[C:20]([CH2:19][NH:18][C:16](=[O:17])[C:15]3[CH:40]=[CH:41][CH:42]=[C:13]([S:10]([N:9]([CH3:43])[CH2:8][C:4]4[CH:3]=[C:2]([C:62]5[CH:61]=[CH:60][CH:59]=[C:58]([CH2:57][N:54]6[CH2:55][CH2:56][NH:51][C@@H:52]([CH3:67])[CH2:53]6)[CH:63]=5)[CH:7]=[CH:6][CH:5]=4)(=[O:12])=[O:11])[CH:14]=3)[C:21]([NH:33][CH:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[C:22]2[CH:30]=[N:29]1)[CH3:32]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 578132803-{[[(3-Bromophenyl)methyl](methyl)amino]sulfonyl}-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}benzamideHCID 67006555{3-[((3R)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]phenyl}boronic acid

Product 1

HCID 57813534N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-3-({methyl[(3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]amino}sulfonyl)benzamideYield 30.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

To a solution of 3-{[[(3-bromophenyl)methyl](methyl)amino]sulfonyl}-N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}benzamide (120 mg, 0.179 mmol) in 1,4-dioxane (3 mL) and H2O (1 mL) was added {3-[((3R)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]phenyl}boronic acid (59.9 mg, 0.179 mmol), Pd(Ph3P)4 (10.35 mg, 8.96 μmol), and K2CO3 (74.3 mg, 0.538 mmol) and the reaction was heated in microwave at 130° C. for 15 min. The organic layer was separated, filtered, concentrated, and purified using a Gilson HPLC (with 0.1% TFA). Before the sample was concentrated with a GeneVac EZ-2, TFA (5 drops) was added to each tube (12 mL). The resultant mixture was concentrated, purified using a Gilson HPLC (with 0.1% TFA), concentrated, and basified with amino cartridge to afford 0.0429 g (30%) of the title compound. LC-MS m/z 779 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 1.35-1.45 (m, 6 H) 1.48 (t, J=7.28 Hz, 3 H) 1.82-1.96 (m, 2 H) 2.10 (d, J=12.55 Hz, 2 H) 2.66 (s, 3 H) 3.18 (q, J=7.61 Hz, 3 H) 3.33-3.39 (m, 1 H) 3.42-3.53 (m, 1 H) 3.60-3.79 (m, 6 H) 3.98-4.10 (m, J=8.41, 3.14 Hz, 2 H) 4.27 (s, 2 H) 4.31-4.40 (m, 1 H) 4.41-4.54 (m, 4 H) 4.75 (s, 2 H) 7.31-7.37 (m, 1 H) 7.40-7.65 (m, 5 H) 7.68-7.85 (m, 3 H) 8.05 (d, J=7.28 Hz, 1 H) 8.23 (d, J=7.78 Hz, 1 H) 8.28 (s, 1 H) 8.39 (s, 1 H).

Workup

  1. customThe organic layer was separated
  2. filtrationfiltered
  3. concentrationconcentrated
  4. custompurified
  5. concentrationBefore the sample was concentrated with a GeneVac EZ-2, TFA (5 drops)
  6. additionwas added to each tube (12 mL)
  7. concentrationThe resultant mixture was concentrated
  8. custompurified
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-cd4c698291854a91909a46b9fc71abf3
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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