Trifluoroacetic acid → N-(2-chloropyridin-4-yl)-8-(cyclopropylamino)-6-(tetrahydro-2H-pyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943507ノート

反応式

HRID 1943507 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([C:11]2[N:15]3[N:16]=[C:17]([NH:33][CH:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH:18]=[C:19]([N:20]([CH:30]4[CH2:32][CH2:31]4)CC4C=CC(OC)=CC=4)[C:14]3=[N:13][CH:12]=2)=[O:10])[CH:5]=[CH:4][N:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([C:11]2[N:15]3[N:16]=[C:17]([NH:33][CH:34]4[CH2:39][CH2:38][O:37][CH2:36][CH2:35]4)[CH:18]=[C:19]([NH:20][CH:30]4[CH2:32][CH2:31]4)[C:14]3=[N:13][CH:12]=2)=[O:10])[CH:5]=[CH:4][N:3]=1

参加物

5

反応物 2

HCID 6422Trifluoroacetic acidHCID 59624640N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)-6-(tetrahydro-2H-pyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide

生成物 1

HCID 59624377N-(2-chloropyridin-4-yl)-8-(cyclopropylamino)-6-(tetrahydro-2H-pyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide収率 44.9%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

A solution of N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)-6-(tetrahydro-2H-pyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (7 mg, 0.013 mmol) in DCM (1 mL) was treated with TFA (0.5 mL, 6.49 mmol) and stirred at room temperature overnight. The reaction mixture was 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=35.169 minutes) was isolated and lyophilized to dryness to afford N-(2-chloropyridin-4-yl)-8-(cyclopropylamino)-6-(tetrahydro-2H-pyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (2.5 mg, 35.9%). 1H NMR 400 MHz, DMSO-D6) δ ppm 11.40 (1H, s), 8.38 (1H, d, J=5.54 Hz), 7.97 (1H, s), 7.75 (1H, s), 7.70 (1H, d, J=5.79 Hz), 7.65 (1H, s), 7.10 (1H, d, J=6.55 Hz), 6.00 (1H, s), 3.85-4.06 (3H, m), 1.93-2.08 (2H, m), 1.43-1.61 (2H, m), 0.71-0.81 (2H, m, J=5.54 Hz), 0.57-0.68 (2H, m). HPLC Rt=4.160 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+]=428.0.

後処理

  1. concentrationThe reaction mixture was concentrated to dryness
  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=35.169 minutes) was isolated

出典と根拠

ORDレコード
ord-c178f481ac00404d963c72a4f1dba6e3
出典データセット
uspto-grants-2013_03
特許番号
US08389527B2

反応ノート

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