Sodium Carbonate → HCID 86715471, compound

HRID 2284563

Reaction equation

HRID 2284563 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:11])=[CH:4][CH:3]=1.[Cl:12][C:13]1[C:18](B2OC(C)(C)C(C)(C)O2)=[CH:17][CH:16]=[CH:15][N:14]=1.C([O-])([O-])=O.[Na+].[Na+].ClC1C(C2C=C3C(=CC=2)NN=C3)=CC=CN=1>O1CCOCC1.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.C(Cl)Cl>[Cl:12][C:13]1[C:18]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[N:7][N:8]3[CH3:11])=[CH:4][CH:3]=2)=[CH:17][CH:16]=[CH:15][N:14]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 120670602-Chloro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 225586756-Bromo-1-methyl-1H-indazoleHCID 86715469HCID 86715469, compound

Product 1

HCID 86715471HCID 86715471, compoundYield 78.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Analogous to the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole,6-(-2-chloropyridin-3-yl)-1-methyl-1H-indazole was prepared by heating the mixture of 6-bromo-1-methyl-1H-indazole (2.0 g, 9.5 mmol), 2-chloro-3-pyridine boronic acid pinacol ester (2.2 g, 9.4 mmol), Pd(PPh3)4 (0.54 g, 0.46 mmol) and 2M aq. Na2CO3 (14 mL, 28 mmol) in 1,4-dioxane (75 mL) under argon atmosphere for 12 h. Upon extractive work-up as discussed in the preparation of 5-(2-chloropyridin-3-yl)-1H-indazole with CH2Cl2 and purification of the concentrate by flash silica gel column chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g, 30-50% EtOAC/hexanes eluting solvent gradient upon dry loading the concentrate absorbed on silica gel) provided 6-(-2-chloropyridin-3-yl)-1-methyl-1H-indazole as a white solid (1.8 g, 77%). 1H NMR (DMSO-d6): δ 8.45 (dd, 1H, J=1.7 and 4.7 Hz), 8.09 (s, 1H), 7.94 (dd, 1H, J=2.0 and 7.6 Hz), 7.82 (d, 1H, J=8.5 Hz), 7.74 (s, 1H), 7.54 (dd, 1H, J=4.7 and 7.6 Hz),7.22 (d, 1H, J=8.5 Hz), 4.06 (s, 3H).LCMS: rt 6.80 min (A), purity 97%, MS (m/e) 244 (MH+)

Workup

  1. customwas prepared
  2. temperatureby heating
  3. concentrationconcentrate by flash silica gel column chromatography (Combiflash® companion System® with RediSep® silica gel column 40 g, 30-50% EtOAC/hexanes eluting solvent gradient
  4. customupon dry loading the concentrate
  5. customabsorbed on silica gel)

Sources & evidence

ORD record
ord-9ad76274fceb4b0f8aad0cc19434fc08
Source dataset
uspto-grants-2015_09
Patent number
US09145433B2

Linked notes

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