Acetic Acid → N-({3'-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylmethyl]-6-fluoro-3-biphenylyl}methyl)-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide

HRID 662130Notes

Reaction equation

HRID 662130 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:48][CH3:49])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:40]5[CH:45]=[CH:44][CH:43]=[C:42]([CH:46]=O)[CH:41]=5)[C:36]([F:39])=[CH:37][CH:38]=4)=[O:30])[N:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2].[C@H:50]12[CH2:56][C@H:53]([NH:54][CH2:55]1)[CH2:52][N:51]2C(OC(C)(C)C)=O.C(O)(=O)C>CS(C)=O>[C@H:50]12[CH2:56][C@H:53]([NH:54][CH2:55]1)[CH2:52][N:51]2[CH2:46][C:42]1[CH:41]=[C:40]([C:35]2[C:36]([F:39])=[CH:37][CH:38]=[C:33]([CH2:32][NH:31][C:29]([C:25]3[CH:26]=[CH:27][CH:28]=[C:23]([C:21]([NH:20][CH2:19][C:10]4[C:11]([NH:12][CH:13]5[CH2:18][CH2:17][O:16][CH2:15][CH2:14]5)=[C:6]5[CH:5]=[N:4][N:3]([CH2:1][CH3:2])[C:7]5=[N:8][C:9]=4[CH2:48][CH3:49])=[O:22])[N:24]=3)=[O:30])[CH:34]=2)[CH:45]=[CH:44][CH:43]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 57819371N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(6-fluoro-3'-formyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide

Product 1

HCID 44192217N-({3'-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-ylmethyl]-6-fluoro-3-biphenylyl}methyl)-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamideYield 18.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(6-fluoro-3′-formyl-3-biphenylyl)methyl]-2,6-pyridinedicarboxamide (50.0 mg. 0.075 mmol) was diluted in DMSO (1.5 mL) and dispensed into a 1 dram vial containing 1,1-dimethylethyl (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (0.226 mmol) and acetic acid (4.52 mg, 0.075 mmol) and fitted magnetic stir bar. The resulting solution was stirred at room temperature for 4 h. MP-B(OAc)3H (0.753 mmol, 176 mg) was added and the solution was stirred for another 12 h. The polymer reagent was filtered off and to the filtrate was added MeOH (2.0 mL) and 1 drop of concentrated HCl. This solution was heated at 60° C.° for 12 h. Purification was completed via a Gilson HPLC (basic conditions) to afford 10.26 mg (18.4%) of the title compound. LC-MS m/z 746 (M+H)+, 0.69 min (ret time).

Workup

  1. customfitted magnetic stir bar
  2. stirringthe solution was stirred for another 12 h
  3. filtrationThe polymer reagent was filtered off and to the filtrate
  4. additionwas added MeOH (2.0 mL) and 1 drop of concentrated HCl
  5. temperatureThis solution was heated at 60° C.° for 12 h
  6. customPurification

Sources & evidence

ORD record
ord-db1e0beafd23408aa23dfa56c10418d6
Source dataset
uspto-grants-2011_12
Patent number
US08084449B2

Reaction notes

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