1,2-Dimethoxyethane → 1-(1,1-Dimethylethyl)-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-6-[6-(4-morpholinyl)-3-pyridinyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 1522409Notes

Reaction equation

HRID 1522409 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]2[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=2[CH3:26])=[O:17])[C:5]2[C:10]([CH3:11])=[N:9][N:8]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=2[N:7]=1.[N:29]1([C:35]2[N:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=2)[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O>[CH3:14][C:12]([N:8]1[C:6]2[N:7]=[C:2]([C:38]3[CH:39]=[N:40][C:35]([N:29]4[CH2:30][CH2:31][O:32][CH2:33][CH2:34]4)=[CH:36][CH:37]=3)[CH:3]=[C:4]([C:16]([NH:18][CH2:19][C:20]3[C:21](=[O:28])[NH:22][C:23]([CH3:27])=[CH:24][C:25]=3[CH3:26])=[O:17])[C:5]=2[C:10]([CH3:11])=[N:9]1)([CH3:13])[CH3:15]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 467351676-(Morpholino)pyridine-3-boronic Acid (contains varying amounts of Anhydride)HCID 565974276-Chloro-1-(1,1-dimethylethyl)-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 565988101-(1,1-Dimethylethyl)-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-6-[6-(4-morpholinyl)-3-pyridinyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Procedure

The title compound was prepared in the same manner as described in example 74 using 6-chloro-1-(1,1-dimethylethyl)-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (70 mg, 0.174 mmol), [6-(4-morpholinyl)-3-pyridinyl]boronic acid (47.1 mg, 0.226 mmol), DME (3 mL), water (1.00 mL), sodium carbonate (0.261 mL, 0.523 mmol) and PdCl2(dppf)-CH2Cl2 adduct (11.38 mg, 0.014 mmol) wherein the reaction time was 40 min. The crude product was purified by column chromatography (eluent: gradient of 0 to 15% (9:1 MeOH/NH4OH)/DCM). The final product was collected as a solid, 61 mg (65%). LCMS E-S (M+H)=530.0 1H NMR (400 MHz, DMSO-d6) δ ppm 1.78 (s, 9 H), 2.12 (s, 3 H), 2.24 (s, 3 H), 2.38 (s, 3 H), 3.52-3.64 (m, 4 H), 3.68-3.80 (m, 4 H), 4.38 (d, J=5.05 Hz, 2 H), 5.88 (s, 1 H), 6.99 (d, J=9.09 Hz, 1 H), 7.61 (s, 1 H), 8.34 (dd, J=8.84, 2.53 Hz, 1 H), 8.68 (t, J=5.05 Hz, 1 H), 8.97 (d, J=2.27 Hz, 1 H), 11.53 (s, 1H).

Workup

  1. customThe crude product was purified by column chromatography (eluent: gradient of 0 to 15% (9:1 MeOH/NH4OH)/DCM)
  2. customThe final product was collected as a solid, 61 mg (65%)

Sources & evidence

ORD record
ord-9e33eb8ce97a4afebac894902d56814f
Source dataset
uspto-grants-2015_07
Patent number
US09073924B2

Reaction notes

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