Diisopropylethylamine → 4-(((1R)-2-fluoro-1,2-dimethylpropyl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 1507911노트

반응식

HRID 1507911 반응식
Cl[C:2]1[C:3]2[N:4]([CH:11]=[CH:12][CH:13]=2)[N:5]=[CH:6][C:7]=1[C:8]([NH2:10])=[O:9].Cl.[F:15][C:16]([CH3:21])([CH3:20])[C@H:17]([NH2:19])[CH3:18].C(N(C(C)C)CC)(C)C>CN1C(=O)CCC1.CO>[F:15][C:16]([CH3:21])([CH3:20])[C@H:17]([NH:19][C:2]1[C:3]2[N:4]([CH:11]=[CH:12][CH:13]=2)[N:5]=[CH:6][C:7]=1[C:8]([NH2:10])=[O:9])[CH3:18]

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 679656194-Chloropyrrolo[1,2-b]pyridazine-3-carboxamideHCID 86677913(2R)-3-fluoro-3-methylbutan-2-amine hydrochloride

생성물 1

HCID 683494474-(((1R)-2-fluoro-1,2-dimethylpropyl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide수율 33%

시약·촉매·용매 2

HCID 887Methanol용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

A solution of 4-chloropyrrolo[1,2-b]pyridazine-3-carboxamide (Preparation 3, 50 mg, 0.26 mmol), (R)-2-Fluoro-1,2-dimethyl-propylamine hydrochloride salt (47 mg, 0.33 mmol, from step 3), and diisopropylethylamine (0.089 mL, 0.51 mmol) in NMP (0.5 mL) was heated to 100° C. for 1 hour in the CEM microwave. The mixture was cooled to rt, diluted with MeOH and purified by reverse-phase Prep HPLC (condition A). The fraction containing the major product was concentrated on the rotovap to remove the MeOH and the aqueous slurry of the product was neutralized by addition of ˜1 mL of saturated aq sodium bicarbonate. Sonication of the slurry followed by vacuum filtration and air drying in the funnel afforded 22 mg (33%) of a pale yellow solid as the title compound. HPLC (condition A): retention time=7.70 min. LCMS (condition B): m/z 265.2. 1H NMR (500 MHz, CD3OD) δ ppm 10.74 (1 H, br. s.), 8.16 (1 H, s), 7.41-7.80 (1 H, m), 7.01 (1 H, dd, J=4.72, 1.39 Hz), 6.72 (1 H, dd, J=4.58, 2.64 Hz), 4.28-4.64 (1 H, m), 1.46-1.55 (6 H, m), 1.44 (3 H, d).

후처리

  1. custompurified by reverse-phase Prep HPLC (condition A)
  2. additionThe fraction containing the major product
  3. concentrationwas concentrated on the rotovap
  4. customto remove the MeOH
  5. additionthe aqueous slurry of the product was neutralized by addition of ˜1 mL of saturated aq sodium bicarbonate
  6. customSonication of the slurry
  7. filtrationfollowed by vacuum filtration and air
  8. customdrying in the funnel

출처 및 근거

ORD 기록
ord-2fcbece341fd4f7f96e1dfab3fecd95c
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09221826B2

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