Trifluoroacetic acid → HCID 59624618, compound

HRID 1943502Notes

Reaction equation

HRID 1943502 reaction equation
Cl[C:2]1[CH:3]=[C:4]([N:21]([CH:31]2[CH2:33][CH2:32]2)CC2C=CC(OC)=CC=2)[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.[CH3:34][N:35]1[CH2:40][CH2:39][CH:38]([NH2:41])[CH2:37][CH2:36]1.CN1C(=O)CCC1.C(O)(C(F)(F)F)=O>CO.C(Cl)Cl>[CH:31]1([NH:21][C:4]2[C:5]3[N:6]([C:8]([C:11]([NH:13][C:14]4[CH:19]=[CH:18][N:17]=[CH:16][C:15]=4[F:20])=[O:12])=[CH:9][N:10]=3)[N:7]=[C:2]([NH:41][CH:38]3[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH2:37]3)[CH:3]=2)[CH2:32][CH2:33]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 13387N-methyl-2-pyrrolidoneHCID 27375314-Amino-1-methylpiperidineHCID 86649272HCID 86649272, compound

Product 1

HCID 59624618HCID 59624618, compoundYield 26.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A microwave tube was charged with 6-chloro-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (35 mg, 0.075 mmol), 1-methylpiperidin-4-amine (86 mg, 0.750 mmol) and NMP (1 mL). The reaction mixture was irradiated in a microwave (300 W) for 20 minutes at 100° C. The crude reaction mixture 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, 30 min gradient, monitored at 220 nm). The product (retention time=30.463 minutes) was isolated and lyophilized to dryness. The crude material was dissolved in CH2Cl2 (2 mL) and treated with TFA (0.5 mL) and stirred at room temperature for 2 hours, then concentrated to dryness. 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, 30 min gradient, monitored at 220 nm). The product (retention time=24.643 minutes) was isolated and lyophilized to dryness to afford 8-(cyclopropylamino)-N-(3-fluoropyridin-4-yl)-6-(1-methylpiperidin-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (8.5 mg, 14.42%). HPLC Rt=2.681 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+]=425.0.

Workup

  1. customThe reaction mixture was irradiated in a microwave (300 W) for 20 minutes at 100° C
  2. customThe crude reaction mixture
  3. custompurified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 30 min gradient, monitored at 220 nm)
  4. customThe product (retention time=30.463 minutes) was isolated
  5. concentrationconcentrated to dryness
  6. customThe crude reaction product
  7. custompurified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 30 min gradient, monitored at 220 nm)
  8. customThe product (retention time=24.643 minutes) was isolated

Sources & evidence

ORD record
ord-786c47c63ae04350abcc98f91a389ca4
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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