1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 178446174, 화합물

HRID 730536노트

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HRID 730536 반응식
C(O[C:4]([C:6]1[C:11](=[O:12])[N:10]([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[N:9]2[CH:18]=[C:19]([C:21]#[N:22])[CH:20]=[C:8]2[C:7]=1[OH:23])=O)C.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][S:32]([CH3:35])(=[O:34])=[O:33])=[CH:27][C:26]=1[S:36]([NH2:39])(=[O:38])=[O:37].N12CCCN=C1CCCCC2>N1C=CC=CC=1>[C:21]([C:19]1[CH:20]=[C:8]2[C:7]([OH:23])=[C:6]([C:4]3[NH:24][C:25]4[CH:30]=[CH:29][C:28]([NH:31][S:32]([CH3:35])(=[O:33])=[O:34])=[CH:27][C:26]=4[S:36](=[O:38])(=[O:37])[N:39]=3)[C:11](=[O:12])[N:10]([CH2:13][CH2:14][CH:15]([CH3:16])[CH3:17])[N:9]2[CH:18]=1)#[N:22]

참가 물질

5

반응물 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 249506572-Amino-5-[(methylsulfonyl)amino]benzenesulfonamideHCID 598535636-Cyano-4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazine-3-carboxylic acid ethyl ester

생성물 1

HCID 178446174HCID 178446174, 화합물수율 6.7%

시약·촉매·용매 1

HCID 1049Pyridine용매

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온도
120 °C

실험 절차

A solution of 6-cyano-4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazine-3-carboxylic acid ethyl ester (Example 15e, 0.25 g, 0.788 mmol) and 2-amino-5-methanesulfonylamino-benzenesulfonamide (Example 3d, 0.209 g, 0.788 mmol) in pyridine (4 mL) was heated to 120° C. for 3 h. 1,8-Diazabicyclo[5.4.0]undec-7-ene (200 μL) was added and the mixture was heated at 120° C. for 16 h. The reaction mixture was passed through a plug of silica gel and eluted with 50%→100% ethyl acetate in hexanes. The solvents were removed in vacuo and purification by preparative HPLC (Column Luna 5μ C18 (2) 100 Å size 150×21.2 mm, 5 micron, 40%-95% in 11 min 25 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water) afforded the desired product, N-{3-[6-cyano-4-hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.0275 g, 0.0531 mmol, 6.7% yield). 1H NMR (400 MHz, DMSO-d6) δ: 0.94 (3H, s), 0.96 (3H, s), 1.17-1.23 (2H, m), 1.51-1.57 (2H, m), 1.65-1.75 (1H, m), 5.74 (1H, s), 3.05 (3H, s), 7.40 (1H, s), 7.49-7.57 (3H, m), 8.51 (1H, s), 10.12 (1H, s), 13.75 (1H, s). LC-MS (ESI) calcd for C21H22N6O6S2 518.10, found 519.4 [M+H+].

후처리

  1. washeluted with 50%→100% ethyl acetate in hexanes
  2. customThe solvents were removed in vacuo and purification by preparative HPLC (Column Luna 5μ C18 (2) 100 Å size 150×21.2 mm, 5 micron, 40%-95% in 11 min 25 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water)

출처 및 근거

ORD 기록
ord-b002757790714cf4947cb026845b2f75
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582754B2

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