Diisopropylethylamine → ethyl 4-((1R,3S)-3-amino-2,2,3-trimethylcyclopentylamino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate

HRID 1408921노트

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HRID 1408921 반응식
C(N(CC)C(C)C)(C)C.[C:10]([C:13]1[CH:18]=[N:17][N:16]2[CH:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=[C:15]2[C:14]=1Cl)(=[O:12])[NH2:11].[CH3:28][C@:29]1([NH2:37])[CH2:33][CH2:32][C@@H:31]([NH2:34])[C:30]1([CH3:36])[CH3:35]>CN(C)C=O>[NH2:37][C@@:29]1([CH3:28])[CH2:33][CH2:32][C@@H:31]([NH:34][C:14]2[C:15]3[N:16]([CH:19]=[C:20]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:21]=3)[N:17]=[CH:18][C:13]=2[C:10](=[O:12])[NH2:11])[C:30]1([CH3:36])[CH3:35]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 24271783(1S,3R)-1,2,2-trimethylcyclopentane-1,3-diamineHCID 68290691Ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate

생성물 1

HCID 68358616ethyl 4-((1R,3S)-3-amino-2,2,3-trimethylcyclopentylamino)-3-carbamoylpyrrolo[1,2-b]pyridazine-6-carboxylate수율 44.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

N,N-Diisopropylethylamine (7.18 mL, 41.1 mmol) was added to a mixture of ethyl 3-carbamoyl-4-chloropyrrolo[1,2-b]pyridazine-6-carboxylate (3.67 g, 13.71 mmol, from Preparation 4), (1S,3R)-1,2,2-trimethylcyclopentane-1,3-diamine (2.93 g, 20.57 mmol, prepared according to conditions described in Tetrahedron Asymmetry 2001, 12, 1579 and Eur. J. Inorg. Chem. 2006, 839) and N,N-dimethylformamide (50 mL). The mixture was stirred in a 90° C. oil bath for 1 h, quenched with saturated sodium bicarbonate (250 mL) and extracted with ethyl acetate (4×200 mL). The combined extracts were dried (MgSO4), filtered, concentrated and pumped under vacuum. The solid residue was treated with ethyl acetate (60 mL) and sonicated for 10 min. Vacuum filtration gave the first batch of the title compound (2.292 g). The filtrate was concentrated to dryness. The solid residue was treated with dichloromethane (5 mL), ethyl acetate (4 mL) and hexanes (16 mL). The mixture was sonicated for 15 min and filtered. The solid was washed with 20% ethyl acetate in hexanes to give second batch of the title compound (2.146 g). The combined amount of the title compound was 4.438 g (87% yield). 1H NMR (500 MHz, methanol-d4) δ ppm 8.19 (1 H, s), 8.00 (1 H, d, J=1.66 Hz), 7.33 (1 H, d, J=1.66 Hz), 4.47 (1 H, t, J=8.18 Hz), 4.35 (2 H, q, J=7.03 Hz), 2.21-2.49 (1 H, m), 1.77-1.93 (2 H, m), 1.63-1.75 (1 H, m), 1.38 (3 H, t, J=7.21 Hz), 1.21 (3 H, s), 1.07 (3 H, s), 0.96 (3 H, s); MS (ES+) m/z: 374.2 (M+H); HPLC retention time: 2.975 min (analytical HPLC Method F).

후처리

  1. customquenched with saturated sodium bicarbonate (250 mL)
  2. extractionextracted with ethyl acetate (4×200 mL)
  3. dry with materialThe combined extracts were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. additionThe solid residue was treated with ethyl acetate (60 mL)
  7. customsonicated for 10 min
  8. filtrationVacuum filtration

출처 및 근거

ORD 기록
ord-820980b83f6144208e583d1c2a4c5509
출처 데이터셋
uspto-grants-2014_12
특허 번호
US08921368B2

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