Hydrochloric Acid → HCID 67365385, compound

HRID 2046941Notes

Reaction equation

HRID 2046941 reaction equation
C1C2C(COC(=O)N[C@H](C([N:25]3[C:29]4=[N:30][CH:31]=[C:32](Br)[CH:33]=[C:28]4[C:27]([C@@H:35]([C:37]4[C:42]([Cl:43])=[CH:41][CH:40]=[C:39]([F:44])[C:38]=4[Cl:45])[CH3:36])=[CH:26]3)=O)CC(C)C)C3C(=CC=CC=3)C=2C=CC=1.O1CCCCC1[O:53][CH2:54][CH2:55][N:56]1[CH:60]=[C:59](B2OC(C)(C)C(C)(C)O2)[CH:58]=[N:57]1.C(=O)([O-])[O-].[K+].[K+].Cl>O1CCOCC1.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.O>[Cl:45][C:38]1[C:39]([F:44])=[CH:40][CH:41]=[C:42]([Cl:43])[C:37]=1[C@H:35]([C:27]1[C:28]2[C:29](=[N:30][CH:31]=[C:32]([C:59]3[CH:58]=[N:57][N:56]([CH2:55][CH2:54][OH:53])[CH:60]=3)[CH:33]=2)[NH:25][CH:26]=1)[CH3:36]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 58431443HCID 58431443, compoundHCID 593418191-[2-(oxan-2-yloxy)ethyl]-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Product 1

HCID 67365385HCID 67365385, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
85 °C

Procedure

A mixture of ((S)-1-{5-bromo-3-[(S)-1-(2,6-dichloro-3-fluorophenyl)ethyl]pyrrolo[2,3-b]pyridine-1-carbonyl}-3-methylbutyl)-carbamic acid 9H-fluoren-9-ylmethyl ester (190.0 mg, 0.262 mmol), 1-[2-(tetrahydropyran-2-yloxy)ethyl]-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (95.0 mg, 0.294 mol), Pd(PPh3)4 (20 mg, 0.010 mmol), potassium carbonate (181 mg, 1.31 mmol) in a mixed solvent of dioxane and water (v:v=4:1, dioxane:H2O, 10 mL) was heated to 85° C. for 1 h. The organic solvent was removed and the material was transferred to a separatory funnel and extracted with DCM (20 mL×3). The organic layers were combined, dried (Na2SO4) and concentrated in vacuo to give a residue that was re-dissolved in dioxane (4 mL). 2M aq. HCl (1.0 mL) was added at rt, and the solution was allowed to stir for 1 h. The solvents were removed in vacuo, and the material was dry-loaded onto silica gel for column chromatography, eluting with 3-4% (7N NH3 in MeOH)/DCM to reveal the title compound. MS (ES+): m/z=419.21, 421.19 (100, 85) [MH+]. HPLC: tR=0.92 min (HPLC-ACQUITY, Purity).

Workup

  1. customThe organic solvent was removed
  2. customthe material was transferred to a separatory funnel
  3. extractionextracted with DCM (20 mL×3)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto give a residue that
  7. customThe solvents were removed in vacuo
  8. washeluting with 3-4% (7N NH3 in MeOH)/DCM

Sources & evidence

ORD record
ord-ac8603caadaa49ed846b841e365d1785
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

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