Dichloromethane → HCID 54674514, compound

HRID 2095683Notes

Reaction equation

HRID 2095683 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([CH3:8])[C:6]=1[Cl:7].[Cl:9][C:10]1[C:15]([F:16])=[CH:14][CH:13]=[C:12]([O:17][CH3:18])[C:11]=1[C@H:19]([C:21]1[C:29]2[C:24](=[N:25][CH:26]=[C:27](B3OC(C)(C)C(C)(C)O3)[CH:28]=2)[NH:23][CH:22]=1)[CH3:20].C(=O)([O-])[O-].[K+].[K+].ClCCl>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].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:9][C:10]1[C:15]([F:16])=[CH:14][CH:13]=[C:12]([O:17][CH3:18])[C:11]=1[C@H:19]([C:21]1[C:29]2[C:24](=[N:25][CH:26]=[C:27]([C:2]3[CH:3]=[N:4][N:5]([CH3:8])[C:6]=3[Cl:7])[CH:28]=2)[NH:23][CH:22]=1)[CH3:20]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 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]pyridineHCID 670046084-bromo-5-chloro-1-methyl-1H-pyrazole2×

Product 1

HCID 54674514HCID 54674514, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-bromo-5-chloro-1-methyl-1H-pyrazole (10.2 mg, 0.0522 mmol), 3-[(S)-1-(2-chloro-3-fluoro-6-methoxy-phenyl)-ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (15 mg, 0.035 mmol), potassium carbonate (14.4 mg, 0.104 mmol), and 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride, dichloromethane (1.42 mg, 0.00174 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]. The reaction was then charged with an additional 4-bromo-5-chloro-1-methyl-1H-pyrazole (10.2 mg, 0.0522 mmol) and charged with Pd(PPh3)4 (2.01 mg, 0.00174 mmol) and evacuated and charged with N2 (2×) and heated under microwave conditions [Biotage, 100° C., 30 min, high absorption]. A small water layer was removed from MW vial and the crude sample was purified by HPLC resulting the title compound as an off-white solid. 1H NMR (400 MHz, CD3OD): δ=1.80 (d, J=7.1 Hz, 3H), 3.64 (br. s., 3H), 3.88 (s, 3H), 5.11 (d, J=6.8 Hz, 1H), 6.89 (dd, J=4.0, 8.6 Hz, 1H), 7.08 (dd, J=8.8, 8.8 Hz, 1H), 7.35 (s, 1H), 7.65-7.73 (m, 2H), 8.22-8.29 (m, 1H). MS (ES+): m/z 419.05, 421.03 (76/24) [MH+]. HPLC: tR=3.70 min (polar—5 min, ZQ3).

Workup

  1. customwater (1.0 mL) was evacuated
  2. additioncharged with N2 (2×)
  3. customevacuated
  4. additioncharged with N2 (2×)
  5. temperatureheated under microwave conditions [Biotage, 100° C., 30 min, high absorption]
  6. customA small water layer was removed from MW vial
  7. customthe crude sample was purified by HPLC

Sources & evidence

ORD record
ord-bf13c1fd3e294aafa32faa10ea2f30e0
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

Loading…