Trifluoroacetic acid → HCID 59624494, compound

HRID 1943503Notes

Reaction equation

HRID 1943503 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.[CH2:34]1[CH2:41][CH:40]([NH2:42])[C:38](=[O:39])[NH:37][CH2:36][CH2:35]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:42][CH:40]3[CH2:41][CH2:34][CH2:35][CH2:36][NH:37][C:38]3=[O:39])[CH:3]=2)[CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 13387N-methyl-2-pyrrolidoneHCID 1024632H-Azepin-2-one, 3-aminohexahydro-HCID 86649272HCID 86649272, compound

Product 1

HCID 59624494HCID 59624494, compoundYield 21.3%

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), DL-alpha-Amino-epsilon-caprolactam (96 mg, 0.750 mmol), and NMP (1 mL). The reaction mixture was irradiated (300 W) at 100° C. for 40 minutes. 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=35.053 minutes) was isolated and lyophilized to dryness. The resulting material was dissolved in DCM (2 mL) and treated with TFA (0.5 mL, 6.49 mmol). Reaction was stirred at room temperature for three hours, and 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=30.556 minutes) was isolated and lyophilized to dryness to afford 8-(cyclopropylamino)-N-(3-fluoropyridin-4-yl)-6-(2-oxoazepan-3-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (7 mg, 13.73%). 1H NMR (400 MHz, DMSO) δ ppm 11.24 (1H, s), 8.73 (1H, d, J=2.77 Hz), 8.45 (1H, d, J=5.54 Hz), 8.39 (1H, t), 8.01 (1H, s), 7.84 (1H, t, J=6.04 Hz), 7.66 (1H, s), 6.99 (1H, s), 6.31 (1H, s), 4.54 (1H, d, J=9.57 Hz), 2.98-3.24 (3H, m), 1.80-2.02 (2H, m), 1.67 (1H, d, J=14.10 Hz), 1.37-1.59 (2H, m), 1.20-1.32 (1H, m), 0.73-0.85 (2H, m), 0.54-0.70 (2H, m). HPLC Rt=3.633 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+]=439.0.

Workup

  1. customThe reaction mixture was irradiated (300 W) at 100° C. for 40 minutes
  2. customThe crude reaction product
  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=35.053 minutes) was isolated
  5. customReaction
  6. concentrationconcentrated to dryness
  7. customThe crude reaction product
  8. 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
  9. customThe product (retention time=30.556 minutes) was isolated

Sources & evidence

ORD record
ord-9fa3f6e232804e1b9f41301e28b7c525
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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