Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-{[6-fluoro-3'-(hydroxymethyl)-3-biphenylyl]methyl}-1,3-benzenedicarboxamide

HRID 564490Notes

Reaction equation

HRID 564490 reaction equation
[F:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][OH:15])[CH:9]=2)=[CH:6][C:5]([CH2:16][NH:17][C:18]([C:20]2[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=2)[C:23](O)=[O:24])=[O:19])=[CH:4][CH:3]=1.[NH2:29][CH2:30][C:31]1[C:36]([CH2:37][CH3:38])=[N:35][C:34]2[N:39]([CH2:42][CH3:43])[N:40]=[CH:41][C:33]=2[C:32]=1[NH:44][CH:45]1[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl>[CH2:42]([N:39]1[C:34]2=[N:35][C:36]([CH2:37][CH3:38])=[C:31]([CH2:30][NH:29][C:23]([C:22]3[CH:26]=[CH:27][CH:28]=[C:20]([C:18]([NH:17][CH2:16][C:5]4[CH:6]=[C:7]([C:8]5[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][OH:15])[CH:9]=5)[C:2]([F:1])=[CH:3][CH:4]=4)=[O:19])[CH:21]=3)=[O:24])[C:32]([NH:44][CH:45]3[CH2:46][CH2:47][O:48][CH2:49][CH2:50]3)=[C:33]2[CH:41]=[N:40]1)[CH3:43]

Participants

5

Reactant 3

HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 578135113-[({[6-Fluoro-3'-(hydroxymethyl)-3-biphenylyl]methyl}amino)carbonyl]benzoic acidHCID 596832145-(Aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine

Product 1

HCID 57813265N-{[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-{[6-fluoro-3'-(hydroxymethyl)-3-biphenylyl]methyl}-1,3-benzenedicarboxamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-[({[6-Fluoro-3′-(hydroxymethyl)-3-biphenylyl]methyl}amino)carbonyl]benzoic acid (0.06 g, 0.158 mmol), 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (0.048 g, 0.158 mmol), HBTU (0.06 g, 0.158 mmol), TEA (44 μL, 0.316 mmol) were combined in CH2Cl2 (10 mL) and stirred under argon overnight. Aqueous workup followed by CombiFlash purification on a 12 g column eluted with 0-8% MeOH/CH2Cl2 afforded the title compound. LC-MS m/z 664.8 (M+H)+, 1.80 min (ret time).

Workup

  1. customAqueous workup followed by CombiFlash purification on a 12 g column
  2. washeluted with 0-8% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-4612b12d8aea454ea89e3d8843caad0b
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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