Potassium Carbonate → 7-{(1S)-1-[6-(1-methyl-1H-pyrazol-4-yl) [1,2,4]triazolo[4,3-b]pyridazin-3-yl]ethoxy}-3-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]furo[3,2-c]pyridin-6-amine

HRID 912073Notes

Reaction equation

HRID 912073 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C@@H:11]([O:13][C:14]3[C:15]4[O:23][CH:22]=[C:21]([C:24]5[CH:25]=[N:26][N:27]([CH:29]6[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]6)[CH:28]=5)[C:16]=4[CH:17]=[N:18][C:19]=3[NH2:20])[CH3:12])=[N:9][N:10]=2)[N:7]=1.[CH3:35][N:36]1[CH:40]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:38]=[N:37]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>[CH3:35][N:36]1[CH:40]=[C:39]([C:2]2[CH:3]=[CH:4][C:5]3[N:6]([C:8]([C@@H:11]([O:13][C:14]4[C:15]5[O:23][CH:22]=[C:21]([C:24]6[CH:25]=[N:26][N:27]([CH:29]7[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]7)[CH:28]=6)[C:16]=5[CH:17]=[N:18][C:19]=4[NH2:20])[CH3:12])=[N:9][N:10]=3)[N:7]=2)[CH:38]=[N:37]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 57812738HCID 57812738, compound

Product 1

HCID 578124247-{(1S)-1-[6-(1-methyl-1H-pyrazol-4-yl) [1,2,4]triazolo[4,3-b]pyridazin-3-yl]ethoxy}-3-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]furo[3,2-c]pyridin-6-amine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 7-[(S)-1-(6-Chloro[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethoxy]-3-(1-piperidin-4-yl-1H-pyrazol-4-yl)furo[3,2-c]pyridin-6-ylamine (0.289 mmol, 1 eq), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.507 mmol, 2.7 eq), Pd(PPh3)4 (66.8 mg, 0.0578 mmol, 20 mol %), and K2CO3 (200 mg, 1.45 mmol, 5.0 eq) in a 4:1 ratio of dioxane (4 mL) to H2O (1 mL) was evacuated and charged with nitrogen several times. The reaction sample was then heated in a microwave reactor at 100° C. for 0.5 h. CH2Cl2 and H2O were added and a standard aqueous workup was performed. The crude material was purified by chromatography on an SCX column and HPLC giving the title compound as a diformate salt. 1H NMR (400 MHz, CD3OD): δ=2.15 (d, J=6.8 Hz, 3H), 2.25-2.40 (m, 4H), 3.18-3.28 (ddd, J=12.9, 11.6, 3.8 Hz, 2H), 3.59 (dt, J=13.3, 3.3 Hz, 2H), 3.85 (s, 3H), 4.60 (dddd, J=10.0, 4.9, 4.8 Hz, 1H), 6.34 (q, J=6.6 Hz, 1H), 7.62 (d, J=9.6 Hz, 1H), 7.81 (s, 1H), 7.84 (s, 2H), 8.03 (s, 1H), 8.04 (s, 1H), 8.08 (s, 1H), 8.13 (d, J=9.6 Hz, 1H), 8.34 (br s, 4H). MS (ES+): m/z 526.17 (20) [MH+]. HPLC: tR=1.94 min (ZQ3, polar—5 min).

Workup

  1. customwas evacuated
  2. additioncharged with nitrogen several times
  3. additionCH2Cl2 and H2O were added
  4. customThe crude material was purified by chromatography on an SCX column and HPLC

Sources & evidence

ORD record
ord-537521a02b514c75976d48bc99540129
Source dataset
uspto-grants-2011_09
Patent number
US08022206B2

Reaction notes

Loading…