Cyclohexylamine → HCID 59624868, compound

HRID 1943481Notes

Reaction equation

HRID 1943481 reaction equation
Br[C:2]1[C:3]2[N:4]([C:9]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3[F:21])=[O:13])=[CH:10][N:11]=2)[N:5]=[C:6](Cl)[CH:7]=1.C1COCC1.[CH:27]1([NH2:31])[CH2:30][CH2:29][CH2:28]1.[CH:32]1([NH2:38])[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>CO>[CH:27]1([NH:31][C:2]2[C:3]3[N:4]([C:9]([C:12]([NH:14][C:15]4[CH:20]=[CH:19][N:18]=[CH:17][C:16]=4[F:21])=[O:13])=[CH:10][N:11]=3)[N:5]=[C:6]([NH:38][CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)[CH:7]=2)[CH2:30][CH2:29][CH2:28]1

Participants

6

Reactant 4

HCID 7965CyclohexylamineHCID 8028TetrahydrofuranHCID 75645CyclobutylamineHCID 596244958-Bromo-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

Product 1

HCID 59624868HCID 59624868, compoundYield 18.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

A 1 dram vial was charged with 8A (25 mg, 0.077 mmol) and THF (1 mL). Cyclobutylamine (8.54 μL, 0.100 mmol) was added and the reaction was heated to 80° C. After 4 hours at 80° C., the reaction was cooled to room temperature and the solvent was removed under a stream of nitrogen. Cyclohexylamine (500 μL, 4.37 mmol) was added and the reaction was heated to 140° C. for 12 hours. The crude reaction product was dissolved in a small amount of MeOH and purified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 50 min gradient, monitored at 220 nm). The product (retention time=35.6 minutes) was isolated and lyophilized to dryness to afford 8-(cyclobutylamino)-6-(cyclohexylamino)-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (6 mg, 14.56%). 1H NMR (400 MHz, DMSO-D6) δ ppm 11.33-11.47 (1H, m), 8.71-8.82 (1H, m), 8.51-8.62 (1H, m), 8.41-8.51 (1H, m), 8.01-8.09 (1H, m), 7.42-7.56 (1H, m), 6.69-6.86 (1H, m), 5.65-5.74 (1H, m), 3.89-4.02 (1H, m), 3.78-3.89 (1H, m), 2.28-2.42 (2H, m), 2.05-2.21 (2H, m), 1.87-2.01 (2H, m), 1.64-1.85 (4H, m), 1.53-1.64 (1H, m), 1.13-1.46 (5H, m). HPLC tR=4.775 min (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min gradient, monitored at 220 nm). [M+H+]=424.32.

Workup

  1. temperaturethe reaction was cooled to room temperature
  2. customthe solvent was removed under a stream of nitrogen
  3. temperaturethe reaction was heated to 140° C. for 12 hours
  4. customThe crude reaction product
  5. custompurified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 50 min gradient, monitored at 220 nm)
  6. customThe product (retention time=35.6 minutes) was isolated

Sources & evidence

ORD record
ord-29e56bb8b81b4842b94f08c80542a083
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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