Water → HCID 178472382, compound

HRID 2095648Notes

Reaction equation

HRID 2095648 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C@@H:11]([C:13]3[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[C:15]([F:21])[C:14]=3[Cl:22])[CH3:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.[CH3:23][C:24]1[C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][N:26]([C@H:38]2[CH2:43][CH2:42][C@H:41]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:40][CH2:39]2)[N:25]=1.[F-].[K+].O>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:22][C:14]1[C:15]([F:21])=[CH:16][CH:17]=[C:18]([O:19][CH3:20])[C:13]=1[C@H:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:28]3[C:24]([CH3:23])=[N:25][N:26]([C@H:38]4[CH2:39][CH2:40][C@H:41]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:42][CH2:43]4)[CH:27]=3)[CH:3]=2)[NH:8][CH:9]=1)[CH3:12]

Participants

7

Reactant 4

HCID 962WaterHCID 522689Potassium FluorideHCID 670045375-Bromo-3-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridineHCID 178472380HCID 178472380, compound

Product 1

HCID 178472382HCID 178472382, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-bromo-3-[(S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (57.8 mg, 0.150 mmol), ethyl trans-4-[3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]cyclohexanecarboxylate (60.0 mg, 0.166 mmol), Pd(PPh3)4 (8.70 mg, 0.00753 mmol), potassium fluoride (26.2 mg, 0.452 mmol) and 4:1 dioxane:H2O (3 mL, 30 mmol) was heated to 90° C. for 2 h. The organic solvent was removed in vacuo, and the material was extracted with DCM and water. The organic layer was purified via column chromatography, eluting with 1-3% MeOH/DCM. The fractions containing the pure product were concentrated in vacuo to afford the title compound as a white solid. MS (ES+): m/z=539.18/541.20 (100/50) [MH+]. HPLC: tR=1.70 min (polar—3 min, UPLC-ACQUITY).

Workup

  1. customThe organic solvent was removed in vacuo
  2. extractionthe material was extracted with DCM and water
  3. customThe organic layer was purified via column chromatography
  4. washeluting with 1-3% MeOH/DCM
  5. additionThe fractions containing the pure product
  6. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-77b4a0fe53f649b996ff9e89b2639bd3
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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