Dimethylformamide → Imidazo[1,2-b]pyridazine derivative 7

HRID 588528

반응식

HRID 588528 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([NH2:23])=[CH:21][N:22]=2)[N:19]=1.[CH3:24][S:25]([NH:28][C:29]1[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][CH:30]=1)(=[O:27])=[O:26].CN(C=O)C.CCN(C(C)C)C(C)C>CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([NH:23][C:33](=[O:34])[C:32]3[CH:36]=[CH:37][C:29]([NH:28][S:25]([CH3:24])(=[O:27])=[O:26])=[CH:30][CH:31]=3)=[CH:21][N:22]=2)[N:19]=1

참가 물질

6

반응물 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2506534-(Methylsulfonamido)benzoic acidHCID 58334496(R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-amine

생성물 1

HCID 46182706Imidazo[1,2-b]pyridazine derivative 7수율 27%

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A reaction vial was charged with (R)-6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-amine (Preparation B; 30 mg, 0.095 mmol), 4-(methylsulfonamido)benzoic acid (41 mg, 0.19 mmol), and 2(1H-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uranium hexafluorophophate methanaminium (HATU; 72 mg, 0.19 mmol). DMF (0.8 mL) was added to the mixture to make a solution. The reaction mixture was cooled in an ice bath for 10 minutes before DIEA (0.05 mL, 0.29 mmol) was added dropwise. After addition, reaction was warmed to ambient temperature and stirred overnight. The reaction mixture was diluted with EtOAc (20 mL), washed with water and brine (10 mL each), and concentrated. The crude material was purified by reverse-phase column chromatography, eluting with 5 to 60% acetonitrile/water to yield (R)—N-(6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-4-(methylsulfonamido)benzamide as a yellowish solid (13 mg, 27% yield). MS (apci negative) m/z=511.4 (M−H).

후처리

  1. customA reaction
  2. additionwas added dropwise
  3. additionAfter addition, reaction
  4. washwashed with water and brine (10 mL each)
  5. concentrationconcentrated
  6. customThe crude material was purified by reverse-phase column chromatography
  7. washeluting with 5 to 60% acetonitrile/water

출처 및 근거

ORD 기록
ord-bfa8e53b1a72471eb278f4a2ca18e2bc
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09227975B2

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