Nitrogen → 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]pentanediamide

HRID 657386Notes

Reaction equation

HRID 657386 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:9][NH:10][C:11](=[O:39])[CH2:12][CH2:13][CH2:14][C:15]([NH:17][CH2:18][C:19]2[C:20]([NH:32][CH:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[C:21]3[CH:29]=[N:28][N:27]([CH2:30][CH3:31])[C:22]3=[N:23][C:24]=2[CH2:25][CH3:26])=[O:16])[CH:5]=[CH:6][C:7]=1[F:8].[CH:40]([C:42]1[CH:43]=[C:44](B(O)O)[CH:45]=[CH:46][CH:47]=1)=[O:41].C([O-])([O-])=O.[Na+].[Na+].N#N>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.O>[CH2:30]([N:27]1[C:22]2=[N:23][C:24]([CH2:25][CH3:26])=[C:19]([CH2:18][NH:17][C:15](=[O:16])[CH2:14][CH2:13][CH2:12][C:11]([NH:10][CH2:9][C:4]3[CH:3]=[C:2]([C:46]4[CH:45]=[CH:44][CH:43]=[C:42]([CH:40]=[O:41])[CH:47]=4)[C:7]([F:8])=[CH:6][CH:5]=3)=[O:39])[C:20]([NH:32][CH:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[C:21]2[CH:29]=[N:28]1)[CH3:31]

Participants

8

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 27343563-Formylphenylboronic acidHCID 57819876N-[(3-Bromo-4-fluorophenyl)methyl]-N'-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}pentanediamide

Product 1

HCID 57819891N-{[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]pentanediamideYield 137.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A mixture of N-[(3-bromo-4-fluorophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}pentanediamide (0.92 g, 1.5 mmol), (3-formylphenyl)boronic acid (292.5 mg crude, 1.95 mmol), Na2CO3 (477 mg, 4.5 mmol) in dioxane/water (3:1, 16 mL) was swept with N2 for about 5 min before Pd(PPh3)4 (87 mg, 0.075 mmol) was added. The tube was sealed and irradiated with a microwave reactor for 30 min at 150° C. The same reaction was then repeated at the same scale. The combined mixture was mixed with water (50 mL), washed with EtOAc/Diethyl Ether (1:1, 50 mL, 2×). Purification via a CombiFlash system (EtAc/MeOH/DCM) then provided the desired product (1.3 g in total from two trials). LC-MS m/z 630 (M+H)+.

Workup

  1. additionwas added
  2. customThe tube was sealed
  3. customirradiated with a microwave reactor for 30 min at 150° C
  4. customThe same reaction
  5. washwashed with EtOAc/Diethyl Ether (1:1, 50 mL, 2×)
  6. customPurification via a CombiFlash system (EtAc/MeOH/DCM)

Sources & evidence

ORD record
ord-5478c65afa8049ffb1e97cae49c211bd
Source dataset
uspto-grants-2011_12
Patent number
US08071588B2

Reaction notes

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