Potassium Carbonate → 1-(4-{4-[7-amino-2-(thieno[2,3-d]pyridazin-3-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone diformate

HRID 389554Notes

Reaction equation

HRID 389554 reaction equation
I[C:2]1[CH:7]=[N:6][C:5]([NH2:8])=[C:4]2[O:9][C:10]([C:12]3[C:20]4[C:15](=[CH:16][N:17]=[N:18][CH:19]=4)[S:14][CH:13]=3)=[CH:11][C:3]=12.CC1(C)C(C)(C)OB([C:29]2[CH:30]=[N:31][N:32]([CH:34]3[CH2:39][CH2:38][N:37]([C:40](=[O:42])[CH3:41])[CH2:36][CH2:35]3)[CH:33]=2)O1.[C:44](=O)([O-:46])[O-:45].[K+].[K+]>O1CCOCC1.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH:44]([OH:46])=[O:45].[CH:44]([OH:46])=[O:45].[NH2:8][C:5]1[N:6]=[CH:7][C:2]([C:29]2[CH:30]=[N:31][N:32]([CH:34]3[CH2:35][CH2:36][N:37]([C:40](=[O:42])[CH3:41])[CH2:38][CH2:39]3)[CH:33]=2)=[C:3]2[CH:11]=[C:10]([C:12]3[C:20]4[C:15](=[CH:16][N:17]=[N:18][CH:19]=4)[S:14][CH:13]=3)[O:9][C:4]=12

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 593927031-(4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)piperidin-1-yl)ethanoneHCID 667608664-Iodo-2-(thieno[2,3-d]pyridazin-3-yl)furo[2,3-c]pyridin-7-amine

Product 1

HCID 866624201-(4-{4-[7-amino-2-(thieno[2,3-d]pyridazin-3-yl)furo[2,3-c]pyridin-4-yl]-1H-pyrazol-1-yl}piperidin-1-yl)ethanone diformateYield 52.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-iodo-2-(thieno[2,3-d]pyridazin-3-yl)furo[2,3-c]pyridin-7-amine (7.0 mg, 0.018 mmol), 1-{4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidin-1-yl}ethanone (6.80 mg, 0.0213 mmol), (1,1′-bis-(diphenylphosphino)-ferrocene) palladium dichloride (14.6 mg, 0.020 mmol), and potassium carbonate (6.14 mg, 0.0444 mmol) in 1,4-dioxane (0.5 mL) and water (0.2 mL) was irradiated under microwave heating at 120° C. for 60 min. The sample was passed through a syringe filter and purified by preparative HPLC to afford 5.2 mg (50%) of the title compound as a yellow solid. 1H NMR (400 MHz, CD3OD): δ 10.29 (s, 1H), 9.86 (s, 1H), 8.85 (s, 1H), 8.24 (br s, 2H), 8.19 (s, 1H), 7.95 (s, 1H), 7.90 (s, 1H), 7.71 (s, 1H), 4.70 (d, J=11.87 Hz, 1H), 4.55 (t, J=11.37 Hz, 1H), 4.12 (d, J=13.64 Hz, 1H), 3.33-3.41 (m, 1H), 3.21 (q, J=7.16 Hz, 1H), 2.88 (t, J=13.01 Hz, 1H), 2.18 (s, 3H), 2.12-2.30 (m, 3H); MS (ESI): 460.29 [M+H]+; HPLC tR=2.40 min.

Workup

  1. customwas irradiated under microwave
  2. customThe sample was passed through a syringe
  3. filtrationfilter
  4. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-91c2aad559054c12b676704dd07c1216
Source dataset
uspto-grants-2013_02
Patent number
US08378104B2

Reaction notes

Loading…