Potassium Phosphate, Tribasic → 6-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-4-(((3R,4R)-3-ethyl-1-(methylsulfonyl)piperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

HRID 877757

반응식

HRID 877757 반응식
Br[C:2]1[CH:3]=[C:4]2[C:9]([NH:10][C@@H:11]3[CH2:16][CH2:15][N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:13][C@H:12]3[CH2:21][CH3:22])=[C:8]([C:23]([NH2:25])=[O:24])[CH:7]=[N:6][N:5]2[CH:26]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[N:37][N:38]([CH2:40][CH2:41][C:42]#[N:43])[CH:39]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.O1CCOCC1>[C:42]([CH2:41][CH2:40][N:38]1[CH:39]=[C:35]([C:2]2[CH:3]=[C:4]3[C:9]([NH:10][C@@H:11]4[CH2:16][CH2:15][N:14]([S:17]([CH3:20])(=[O:19])=[O:18])[CH2:13][C@H:12]4[CH2:21][CH3:22])=[C:8]([C:23]([NH2:25])=[O:24])[CH:7]=[N:6][N:5]3[CH:26]=2)[CH:36]=[N:37]1)#[N:43]

참가 물질

6

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 569657334-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-propanenitrileHCID 682911046-bromo-4-(((3R,4R)-3-ethyl-1-(methylsulfonyl)piperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

생성물 1

HCID 682907846-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-4-(((3R,4R)-3-ethyl-1-(methylsulfonyl)piperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide수율 56.9%

시약·촉매·용매 2

HCID 178418807HCID 178418807, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

To a vial charged with 6-bromo-4-(((3R,4R)-3-ethyl-1-(methylsulfonyl)piperidin-4-yl)amino) pyrrolo[1,2-b]pyridazine-3-carboxamide (15 mg, 0.034 mmol), 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propanenitrile (16.68 mg, 0.068 mmol) and PdCl2(dppf)-CH2Cl2 Adduct (3.61 mg, 4.42 μmol) were added 1,4-dioxane (225 μl) and a 2M solution of potassium phosphate (50.6 μl, 0.101 mmol). The suspension was purged with nitrogen for 5 minutes. The vial was sealed and heated at 100° C. for 2 hrs. The reaction mixture was diluted with methanol (10 ml), filtered, and concentrated under reduced pressure. The crude product was purified via preparative HPLC (Column: Waters XBridge C18, 19×200 mm, 5-μm). The collected fractions were combined and dried via centrifugal evaporation, yielding 6-(1-(2-cyanoethyl)-1H-pyrazol-4-yl)-4-(((3R,4R)-3-ethyl-1-(methylsulfonyl)piperidin-4-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (9.3 mg, 0.019 mmol, 56.9% yield) as a white solid. 1H NMR (500 MHz, 1:1 Chloroform-d/Methanol-d4) δ 8.12 (s, 1H), 7.93 (s, 1H), 7.82 (s, 1H), 7.75 (d, J=1.5 Hz, 1H), 6.91 (d, J=1.0 Hz, 1H), 4.48 (t, J=6.4 Hz, 2H), 4.11 (td, J=8.4, 4.0 Hz, 1H), 3.79-3.61 (m, 2H), 3.25-3.17 (m, 1H), 3.05 (t, J=6.4 Hz, 2H), 2.97-2.85 (m, 4H), 2.43-2.34 (m, 1H), 1.88-1.76 (m, 3H), 1.51-1.40 (m, 1H), 1.04-0.97 (m, 3H). LCMS (Method K) m/z 485.0 ([M+H]+). HPLC (Method F) Rt: 1.14 min.

후처리

  1. customThe suspension was purged with nitrogen for 5 minutes
  2. customThe vial was sealed
  3. additionThe reaction mixture was diluted with methanol (10 ml)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified via preparative HPLC (Column: Waters XBridge C18, 19×200 mm, 5-μm)
  7. customdried via centrifugal evaporation

출처 및 근거

ORD 기록
ord-83d8bd8775094ff99710a897992b227b
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987268B2

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