Potassium Carbonate → HCID 178461693, compound

HRID 2046947Notes

Reaction equation

HRID 2046947 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18](B3OC(C)(C)C(C)(C)O3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11].I[C:31]1[CH:32]=[N:33][N:34]([C@H:36]2[CH2:41][CH2:40][C@H:39]([OH:42])[CH2:38][CH2:37]2)[CH:35]=1.C(=O)([O-])[O-].[K+].[K+].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:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:31]3[CH:32]=[N:33][N:34]([C@H:36]4[CH2:41][CH2:40][C@H:39]([OH:42])[CH2:38][CH2:37]4)[CH:35]=3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 670045163-[(S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridineHCID 178521568HCID 178521568, compound

Product 1

HCID 178461693HCID 178461693, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of 3-[(S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (60.0 mg, 0.138 mmol), trans-4-(4-iodo-pyrazol-1-yl)cyclohexanol (52.4 mg, 0.179 mmol), Pd(PPh3)4 (8 mg, 0.007 mmol), potassium carbonate (57.2 mg, 0.414 mmol) and 4:1 dioxane:water (7 mL) was heated to 90° C. for 2 h. The organic solvent was removed in vacuo, and the material was transferred to a separatory funnel, extracting with DCM and sat. NaHCO3 solution. The organic layer was dry-loaded onto silica gel, and column chromatography was used to purify, eluting with 3-4% (7N NH3 in MeOH)/DCM. The resulting solid was triturated with MeOH to give the title compound. 1H NMR (400 MHz, CD3OD): δ=1.47-1.59 (m, 2 H), 1.88 (d, J=6.8 Hz, 3 H), 1.90-2.03 (m, 2H), 2.10-2.22 (m, 4 H), 3.66 (tt, J=10.9, 4.2 Hz, 1 H), 4.17 (tt, J=11.6, 4.0 Hz, 1 H), 5.27 (q, J=7.0 Hz, 1 H), 7.18 (dd, J=8.4, 8.8 Hz, 1 H), 7.38 (d, J=1.3 Hz, 1 H), 7.44 (d, J=2.0 Hz, 1 H), 7.46 (br. s., 1 H), 7.54 (d, J=0.8 Hz, 1 H), 7.87 (d, J=0.8 Hz, 1 H), 8.32 (d, J=2.0 Hz, 1 H). MS (ES+): m/z 473.01/475.04 (100/70) [MH+]. HPLC: tR=3.36 min (ZQ3, polar—5 min). This material was redissolved in DCM. 2.0 M of HCl in Et2O (0.8 mL) was added at rt and stirred for 20 min. The mixture was concentrated in vacuo to afford the title compound as an HCl salt.

Workup

  1. customThe organic solvent was removed in vacuo
  2. customthe material was transferred to a separatory funnel
  3. extractionextracting with DCM and sat. NaHCO3 solution
  4. customto purify
  5. washeluting with 3-4% (7N NH3 in MeOH)/DCM
  6. customThe resulting solid was triturated with MeOH

Sources & evidence

ORD record
ord-a3fefea031e84ea4a257045266b2695a
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

Loading…