Potassium Carbonate → 5-(5-Chloro-1,3-dimethyl-1H-pyrazol-4-yl)-3-[(1S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

HRID 2095689Notes

Reaction equation

HRID 2095689 reaction equation
Br[C:2]1[C:3]([CH3:9])=[N:4][N:5]([CH3:8])[C:6]=1[Cl:7].[Cl:10][C:11]1[C:16]([F:17])=[CH:15][CH:14]=[C:13]([O:18][CH3:19])[C:12]=1[C@H:20]([C:22]1[C:30]2[C:25](=[N:26][CH:27]=[C:28](B3OC(C)(C)C(C)(C)O3)[CH:29]=2)[NH:24][CH:23]=1)[CH3:21].C(=O)([O-])[O-].[K+].[K+]>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.O1CCOCC1>[Cl:7][C:6]1[N:5]([CH3:8])[N:4]=[C:3]([CH3:9])[C:2]=1[C:28]1[CH:29]=[C:30]2[C:22]([C@@H:20]([C:12]3[C:13]([O:18][CH3:19])=[CH:14][CH:15]=[C:16]([F:17])[C:11]=3[Cl:10])[CH3:21])=[CH:23][NH:24][C:25]2=[N:26][CH:27]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 197442234-bromo-5-chloro-1,3-dimethyl-1H-pyrazoleHCID 670040713-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 546743655-(5-Chloro-1,3-dimethyl-1H-pyrazol-4-yl)-3-[(1S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-bromo-5-chloro-1,3-dimethyl-1H-pyrazole (0.0219 g, 0.104 mmol), 3-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (0.030 g, 0.070 mmol), potassium carbonate (0.0289 g, 0.209 mmol) and Pd(PPh3)4 (8.04 mg, 0.00697 mmol) in previously degassed 4:1 dioxane:water (1.50 mL) was evacuated and charged with N2 (2×) and heated under microwave conditions [Biotage, 100° C., 30 min, high absorption]. This was further purified by Gilson HPLC resulting in the title compound as white solid. 1H NMR (400 MHz, CD3OD): δ=1.82 (d, J=7.3 Hz, 3H), 2.13 (s, 3H), 3.66 (br. s., 3H), 3.84 (s, 3H), 5.12 (q, J=7.2 Hz, 1H), 6.91 (dd, J=4.2, 9.0 Hz, 1H), 7.09 (dd, J=8.8, 8.8 Hz, 1H), 7.39 (d, J=1.3 Hz, 1H), 7.45 (s, 2H). MS (ES+): m/z 433.03, 435.01 (76/24) [MH+]. HPLC: tR=4.25 min (polar—5 min, ZQ3).

Workup

  1. customwater (1.50 mL) was evacuated
  2. additioncharged with N2 (2×)
  3. customThis was further purified by Gilson HPLC

Sources & evidence

ORD record
ord-a266cb61ff3f4b47a9584740d8e3dd6e
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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