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

HRID 1943505노트

반응식

HRID 1943505 반응식
[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][S: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][S: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

참가 물질

5

반응물 2

HCID 6422Trifluoroacetic acidHCID 59624712N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)-6-(tetrahydro-2H-thiopyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide

생성물 1

HCID 59624512N-(2-chloropyridin-4-yl)-8-(cyclopropylamino)-6-(tetrahydro-2H-thiopyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide수율 13.6%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

A solution of N-(2-chloropyridin-4-yl)-8-(cyclopropyl(4-methoxybenzyl)amino)-6-(tetrahydro-2H-thiopyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (27 mg, 0.048 mmol) in DCM (0.5 mL) was treated with TFA (1.0 mL, 12.98 mmol) and stirred at room temperature for 1 hour 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 254 nm). The product (retention time=36.913 minutes) was isolated and lyophilized to dryness to afford N-(2-chloropyridin-4-yl)-8-(cyclopropylamino)-6-(tetrahydro-2H-thiopyran-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (2.9 mg, 8.33%). HPLC Rt=4.481 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+]=443.9.

후처리

  1. concentrationconcentrated 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 254 nm)
  4. customThe product (retention time=36.913 minutes) was isolated

출처 및 근거

ORD 기록
ord-2732695015044684b08531afeb9fc3ca
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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