Water → HCID 178474335, compound

HRID 1943429Notes

Reaction equation

HRID 1943429 reaction equation
Cl[C:2]1[CH:3]=[C:4]([N:21](CC2C=CC(OC)=CC=2)[C:22](=[O:24])[CH3:23])[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][C:15]=3[F:20])=[O:12])=[CH:9][N:10]=2)[N:7]=1.[C@H:34]1([NH2:41])[CH2:39][CH2:38][C@H:37]([NH2:40])[CH2:36][CH2:35]1.O>CN1C(=O)CCC1>[C:22]([NH:21][C:4]1[C:5]2[N:6]([C:8]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][C:15]=3[F:20])=[O:12])=[CH:9][N:10]=2)[N:7]=[C:2]([NH:40][C@H:37]2[CH2:38][CH2:39][C@H:34]([NH2:41])[CH2:35][CH2:36]2)[CH:3]=1)(=[O:24])[CH3:23]

Participants

5

Reactant 3

HCID 962WaterHCID 59624715HCID 59624715, compoundHCID 178511674HCID 178511674, compound

Product 1

HCID 178474335HCID 178474335, compoundYield 26.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 6-chloro-N-(3-fluoropyridin-4-yl)-8-(N-(4-methoxybenzyl)acetamido)imidazo[1,2-b]pyridazine-3-carboxamide 19B (30 mg, 0.064 mmol) and trans-cyclohexane-1,4-diamine (14.61 mg, 0.128 mmol) in NMP (0.5 mL) was heated at 70° C. for 2.5 h, and then cooled to room temperature. Water was added. The mixture was extracted with EtOAc for three times, the combined extracts were washed with H2O and brine, and then concentrated. The resulting residue was treated with MeOH. The solid was filtered off, and the filtrate was purified by preparative HPLC. The desired fraction was concentrated to dryness and then dissolved in TFA (1 mL). The solution was stirred at 70° C. for 6 h and then concentrated. The residue was treated with MeOH/DCM, and concentrated again to give a solid, which was triturated with ether. The solid was collected by filtration, rinsed with ether, and dried under vacuum to give 19C (7.3 mg, 21%) as an off white solid. [M+H]=427. HPLC Peak Rt=2.018 minutes. (Chromolith column 4.6×50 mm eluting with 10-90% aqueous methanol over 4 minutes containing 0.1% TFA, 4 mL/min, monitoring at 220 nm.)

Workup

  1. extractionThe mixture was extracted with EtOAc for three times
  2. washthe combined extracts were washed with H2O and brine
  3. concentrationconcentrated
  4. additionThe resulting residue was treated with MeOH
  5. filtrationThe solid was filtered off
  6. customthe filtrate was purified by preparative HPLC
  7. concentrationThe desired fraction was concentrated to dryness
  8. dissolutiondissolved in TFA (1 mL)
  9. concentrationconcentrated
  10. additionThe residue was treated with MeOH/DCM
  11. concentrationconcentrated again
  12. customto give a solid, which
  13. customwas triturated with ether
  14. filtrationThe solid was collected by filtration
  15. washrinsed with ether
  16. customdried under vacuum

Sources & evidence

ORD record
ord-e4cb89336b08403cac3c3f5daba8015b
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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