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

HRID 1507911ノート

反応式

HRID 1507911 の反応式
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]

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-2fcbece341fd4f7f96e1dfab3fecd95c
出典データセット
uspto-grants-2015_12
特許番号
US09221826B2

反応ノート

読み込み中…