Hydrochloric Acid → Hydrochloric Acid

HRID 2046951Notes

Reaction equation

HRID 2046951 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C@@H:11]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=3[Cl:21])[CH3:12])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.CC1(C)[O:27][C@@H:26]([CH2:28][N:29]2[CH:33]=[C:32](B3OC(C)(C)C(C)(C)O3)[CH:31]=[N:30]2)[CH2:25][O:24]1.C(=O)([O-])[O-].[K+].[K+].[ClH:50]>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:21][C:14]1[C:15]([F:20])=[CH:16][CH:17]=[C:18]([Cl:19])[C:13]=1[C@H:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:32]3[CH:31]=[N:30][N:29]([CH2:28][C@H:26]([OH:27])[CH2:25][OH:24])[CH:33]=3)[CH:3]=2)[NH:8][CH:9]=1)[CH3:12].[ClH:50]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 584314455-Bromo-3-[(S)-1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridineHCID 67253006(S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 2

HCID 313Hydrochloric AcidHCID 46215820HCID 46215820, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-Bromo-3-[(S)-1-(2,6-dichloro-3-fluorophenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridine (45.0 mg, 0.116 mmol), 1-{[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (71.5 mg, 0.232 mmol), Pd(PPh3)4 (7 mg, 0.006 mmol), potassium carbonate (48.1 mg, 0.348 mmol) and 4:1 Dioxane:water (7 mL) was heated to 90° C. for 2 h. The solution was allowed to cool to rt. 2 M of HCl in water (4 mL) was added until pH 2, and the mixture was stirred at rt overnight. The solution was passed through a SCX cartridge that was washed with MeOH, and the product was eluted with 2M NH3 in MeOH. The material was dry-loaded onto silica gel for column chromatography, eluting with 5% (7N NH3 in MeOH)/DCM. The fractions containing the pure product were concentrated in vacuo, redissolved in DCM, and 2.0 M of HCl in Et2O (0.4 mL) was added. The solution was stirred at rt for 20 min and concentrated in vacuo to afford the title compound as an HCl salt. 1H NMR (400 MHz, CD3OD): δ=1.87 (d, J=7.1 Hz, 3 H), 3.52 (dd, J=5.3, 1.3 Hz, 2 H), 3.95-4.02 (m, 1H), 4.13 (dd, J=14.1, 7.6 Hz, 1 H), 4.31 (dd, J=14.0, 4.2 Hz, 1H), 5.27 (q, J=7.1 Hz, 1 H), 7.17 (dd, J=8.6, 8.6 Hz, 1H), 7.35 (d, J=1.3 Hz, 1 H), 7.37 (d, J=2.0 Hz, 1 H), 7.41 (br. s., 1 H), 7.59 (s, 1 H), 7.82 (s, 1 H), 8.31 (d, J=2.0 Hz, 1 H). MS (ES+): m/z=448.99/451.01 (100/68) [MH+]. HPLC: tR=3.05 min (polar—5 min, ZQ3).

Workup

  1. washwas washed with MeOH
  2. washthe product was eluted with 2M NH3 in MeOH
  3. washeluting with 5% (7N NH3 in MeOH)/DCM
  4. additionThe fractions containing the pure product
  5. concentrationwere concentrated in vacuo
  6. dissolutionredissolved in DCM
  7. addition2.0 M of HCl in Et2O (0.4 mL) was added
  8. stirringThe solution was stirred at rt for 20 min
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4d53f166261049f0bd33481b94e32115
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

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