Dichloromethane → 3-[(1S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)ethyl]-5-(5-methoxy-1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine

HRID 2095687Notes

Reaction equation

HRID 2095687 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([CH3:9])[C:6]=1[O:7][CH3:8].[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+].ClCCl>O1CCOCC1>[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]([C:2]3[CH:3]=[N:4][N:5]([CH3:9])[C:6]=3[O:7][CH3:8])[CH:29]=2)[NH:24][CH:23]=1)[CH3:21]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 131312354-Bromo-5-methoxy-1-methyl-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 546745113-[(1S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)ethyl]-5-(5-methoxy-1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-bromo-5-methoxy-1-methyl-1H-pyrazole (0.0133 g, 0.0697 mmol), 3-[(1S)-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 (0.020 g, 0.046 mmol), potassium carbonate (0.0193 g, 0.139 mmol) 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride, dichloromethane (3.79 mg, 0.00464 mmol) in previously degassed 4:1 dioxane:water (1.0 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. The combined fractions were concentrated in vacuo resulting in the title compound an off-white solid. 1H NMR (400 MHz, CD3OD): δ=1.80 (d, J=7.3 Hz, 3H), 3.63 (s, 3H), 3.67 (br. s., 2H), 3.72 (s, 3H), 5.07-5.16 (m, 1H), 6.91 (dd, J=4.2, 9.0 Hz, 1H), 7.10 (dd, J=8.8, 8.8 Hz, 1H), 7.34 (d, J=1.3 Hz, 1H), 7.52 (s, 2H), 7.67 (s, 1H). MS (ES+): m/z 415.09, 417.07 [MH+]. HPLC: tR=3.95 min (polar—5 min, ZQ3)

Workup

  1. customwater (1.0 mL) was evacuated
  2. additioncharged with N2 (2×)
  3. customThis was further purified by Gilson HPLC
  4. concentrationThe combined fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-7af8aac926bd4178abd83baab667f097
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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