Methanol → HCID 178508373, compound

HRID 389586Notes

Reaction equation

HRID 389586 reaction equation
[Si]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH:19]=[C:18]([C:20]3[CH:25]=[N:24][C:23]([NH2:26])=[C:22]4[O:27][C:28](Cl)=[CH:29][C:21]=34)[CH:17]=[N:16]2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.F[C:32]1[CH:33]=[C:34]2[C:40](B3OC(C)(C)C(C)(C)O3)=[CH:39][S:38][C:35]2=[CH:36][N:37]=1.C(=O)([O-])[O-:51].[Na+].[Na+].C[O-].[Na+].CO.Cl.N1C=CC=CC=1>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>[NH2:26][C:23]1[N:24]=[CH:25][C:20]([C:18]2[CH:17]=[N:16][N:15]([C@H:12]3[CH2:11][CH2:10][C@H:9]([OH:8])[CH2:14][CH2:13]3)[CH:19]=2)=[C:21]2[CH:29]=[C:28]([C:40]3[C:34]4[C:35](=[CH:36][N:37]=[C:32]([OH:51])[CH:33]=4)[S:38][CH:39]=3)[O:27][C:22]=12

Participants

10

Reactant 6

HCID 887MethanolHCID 10340Sodium CarbonateHCID 10176127Pyridinium chlorideHCID 10942334Sodium MethoxideHCID 667596065-Fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thieno[2,3-c]pyridineHCID 178455334HCID 178455334, compound

Product 1

HCID 178508373HCID 178508373, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent3×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

A solution of 4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]-2-chlorofuro[2,3-c]pyridin-7-amine (232 mg, 0.520 mmol), 5-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-thieno[2,3-c]pyridine (235 mg, 0.530 mmol), and Pd(PPh3)4 (60.1 mg, 0.0520 mmol) in 1,4-dioxane (2.0 mL) and aqueous 1.0 M sodium carbonate solution (2.0 mL, 2.0 mmol) was heated to 120° C. in a microwave reactor for 60 min. Water (10 mL) was added, and the mixture was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with water (2×10 mL) and brine (10 mL), dried over MgSO4, filtered, and concentrated. The residue was transferred to a sealable vial. To the vial was added sodium methoxide (148 mg, 2.60 mmol) and methanol (5.0 mL, 120 mmol), and the reaction mixture was heated in a microwave at 150° C. for 2 h. Water (10 mL) was added, and the mixture was extracted with EtOAc (3×15 mL). The organic extracts were washed with water (2×10 mL) and brine (10 mL), dried over MgSO4, filtered, and concentrated. The residue was transferred to a vial, to which was added pyridine hydrochloride (613 mg, 5.20 mmol) and water (10.0 mL), and the mixture was heated at 120° C. for 3 h followed by heating in a microwave at 150° C. for 2 h. Purification of the residue by MDPS afforded 25.6 mg (11%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 8.70 (s, 1H), 8.66 (s, 1H), 8.25 (s, 1H), 7.99 (s, 1H), 7.94 (s, 1H), 7.58 (s, 1H), 7.56 (s, 1H), 6.36 (brs, 2H), 4.70 (br s, 1H), 4.19 (tt, J=11.4, 4.0 Hz, 1H), 3.59-3.45 (m, 1H), 2.12-2.04 (m, 2H), 2.02-1.82 (m, 4H), 1.45-1.33 (m, 2H), 1H overlapping with water peak; MS (ESI): 448.31 [M+H]+; HPLC: tR=2.37 min (ZQ3: polar—5 min).

Workup

  1. extractionthe mixture was extracted with EtOAc (3×10 mL)
  2. washThe combined organic extracts were washed with water (2×10 mL) and brine (10 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. extractionthe mixture was extracted with EtOAc (3×15 mL)
  7. washThe organic extracts were washed with water (2×10 mL) and brine (10 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. temperaturethe mixture was heated at 120° C. for 3 h
  12. temperatureby heating in a microwave at 150° C. for 2 h
  13. customPurification of the residue by MDPS

Sources & evidence

ORD record
ord-20e28e5800b74fcaabe5f735a0900243
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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