Hydrochloric Acid → HCID 178482359, compound

HRID 389567Notes

Reaction equation

HRID 389567 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]([NH:26][CH3:27])=[C:22]4[O:28][C:29](Cl)=[CH:30][C:21]=34)[CH:17]=[N:16]2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.CC1(C)C(C)(C)OB([C:40]2[C:48]3[C:43](=[CH:44][N:45]=[CH:46][CH:47]=3)[S:42][CH:41]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].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>[CH3:27][NH: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:30]=[C:29]([C:40]3[C:48]4[C:43](=[CH:44][N:45]=[CH:46][CH:47]=4)[S:42][CH:41]=3)[O:28][C:22]=12

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 667594503-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thieno[2,3-c]pyridineHCID 178482360HCID 178482360, compound

Product 1

HCID 178482359HCID 178482359, compoundYield 70.3%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 4-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-1H-pyrazol-4-yl]-2-chloro-N-methylfuro[2,3-c]pyridin-7-amine (44.3 mg, 0.0961 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thieno[2,3-c]pyridine (33.9 mg, 0.130 mmol), and Pd(PPh3)4 (12.8 mg, 0.0111 mmol) in 1,4-dioxane (0.5 mL) was charged with 1.0 M aqueous sodium carbonate (0.5 mL) and then irradiated in a microwave at 120° C. for 60 min. The reaction mixture was then charged with 4.0 M hydrochloric acid in 1,4-dioxane (0.6 mL) and stirred at rt for 30 min. The suspension was concentrated in vacuo. The residue was partitioned between a mixture of dichloromethane and aqueous sodium bicarbonate and the layers were separated. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. Purification by ISCO chromatography (2 to 10% 7 N ammonia/methanol:dichloromethane) afforded 30.1 mg (69%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 9.40 (s, 1H), 8.79 (s, 1H), 8.65 (s, 2H), 8.23 (s, 1H), 8.08 (s, 1H), 7.95 (d, J=0.76 Hz, 1H), 7.73 (s, 1H), 6.97 (q, J=4.55 Hz, 1H), 4.70 (d, J=4.55 Hz, 1H), 4.19 (tt, J=3.95, 11.59 Hz, 1H), 3.48-3.59 (m, 1H), 3.02 (d, J=4.80 Hz, 3H), 2.07 (d, J=12.13 Hz, 2H), 1.82-2.01 (m, 4H), 1.31-1.46 (m, 2H); MS (ESI): 446.16 [M+H]+; HPLC tR=2.50 min.

Workup

  1. customirradiated in a microwave at 120° C. for 60 min
  2. concentrationThe suspension was concentrated in vacuo
  3. customThe residue was partitioned between a mixture of dichloromethane and aqueous sodium bicarbonate
  4. customthe layers were separated
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by ISCO chromatography (2 to 10% 7 N ammonia/methanol:dichloromethane)

Sources & evidence

ORD record
ord-ffabe93c93f24d27a87adfc070db75e5
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

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