Trifluoroacetic acid → HCID 178522324, 화합물

HRID 1943444노트

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HRID 1943444 반응식
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([N:28]([CH:38]3[CH2:40][CH2:39]3)CC3C=CC(OC)=CC=3)[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([F:27])[CH:22]=4)=[O:19])=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Br[CH2:51][CH2:52][O:53][CH2:54][CH2:55]Br.C(O)(C(F)(F)F)=O>ClCCCl>[CH:38]1([NH:28][C:11]2[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([F:27])[CH:22]=4)=[O:19])=[CH:16][N:17]=3)[N:14]=[C:9]([NH:8][C@H:5]3[CH2:6][CH2:7][C@H:2]([N:1]4[CH2:55][CH2:54][O:53][CH2:52][CH2:51]4)[CH2:3][CH2:4]3)[CH:10]=2)[CH2:39][CH2:40]1

참가 물질

6

반응물 4

HCID 6422Trifluoroacetic acidHCID 21521Bis(2-bromoethyl) etherHCID 81531DiisopropylethylamineHCID 178490955HCID 178490955, 화합물

생성물 1

HCID 178522324HCID 178522324, 화합물수율 40%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

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온도
60 °C

실험 절차

To a solution of 6-((trans)-4-aminocyclohexylamino)-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(2-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (100 mg, 0.184 mmol) in 1,2-dichloroethane (2 mL) was added DIEA (0.128 mL, 0.734 mmol) and 1-bromo-2-(2-bromoethoxy)ethane (42.6 mg, 0.184 mmol), and the reaction solution was stirred at 60° C. for 9 hrs. The reaction mixture was treated with TFA (0.849 mL, 11.02 mmol) at 65° C. for 1 hr, concentrated, diluted with methanol, and purified by HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 30% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA) to obtain 8-(cyclopropylamino)-N-(2-fluoropyridin-4-yl)-6-((trans)-4-morpholinocyclohexylamino)imidazo[1,2-b]pyridazine-3-carboxamide (36.3 mg, 0.073 mmol, 40.0% yield). LC/MS (BEH C18 2.1×50 mm 1.7u, Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2.2 min with 1 min hold time, Flow rate=2 mL/min, detection at 254 nm, Solvent A: 100% water/0.05% TFA; Solvent B: 100% ACN/0.05% TFA). Rt=0.67 minutes. [M+H]=495.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.40 (1H, s), 9.57-9.89 (1H, m), 8.26 (1H, d, J=5.77 Hz), 7.99 (1H, d, J=1.76 Hz), 7.67 (1H, s), 7.60 (1H, s), 7.44 (1H, d, J=4.77 Hz), 6.88-7.14 (1H, m), 5.98 (1H, s), 4.04 (2H, d, J=11.80 Hz), 3.58-3.83 (3H, m), 3.40 (2H, d, J=12.05 Hz), 2.98-3.23 (2H, m), 2.28 (2H, d, J=11.80 Hz), 2.17 (2H, d, J=11.29 Hz), 1.55 (2H, br. s.), 1.35 (2H, br. s.), 0.78 (2H, d, J=6.53 Hz), 0.63 (2H, br. s.)

후처리

  1. concentrationconcentrated
  2. additiondiluted with methanol
  3. custompurified by HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 30% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA)

출처 및 근거

ORD 기록
ord-4b76d6102eea42229fb4c519a38f78db
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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