HOAt → (R)-(4,4-difluorocyclohexyl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone

HRID 1514372ノート

反応式

HRID 1514372 の反応式
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]1[N:9]=[N:10][C:11]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=12.[F:24][C:25]1([F:34])[CH2:30][CH2:29][CH:28]([C:31](O)=[O:32])[CH2:27][CH2:26]1.Cl.C(N=C=NCCCN(C)C)C.N1C2C(=NC=CC=2)N(O)N=1.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)(=O)C.CCCCCC>[F:24][C:25]1([F:34])[CH2:30][CH2:29][CH:28]([C:31]([N:6]2[CH2:5][CH2:4][N:3]([C:8]3[N:9]=[N:10][C:11]([C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)=[C:12]4[CH:17]=[CH:16][N:15]=[CH:14][C:13]=34)[C@H:2]([CH3:1])[CH2:7]2)=[O:32])[CH2:27][CH2:26]1

参加物

9

反応物 5

HCID 181649HOAtHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27791364,4-Difluorocyclohexanecarboxylic acidHCID 57657605(R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazine

生成物 1

HCID 25226575(R)-(4,4-difluorocyclohexyl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 8058Hexane溶媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

(R)-4-(2-methylpiperazin-1-yl)-1-phenylpyrido[3,4-d]pyridazine 16 (150 mg, 491 μmol), 4,4-difluorocyclohexanecarboxylic acid (88.7 mg, 540 μmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (113 mg, 589 μmol), 3H-[1,2,3]triazolo[4,5-b]pyridin-3-ol (80.2 mg, 589 μmol), sodium bicarbonate (82.5 mg, 982 μmol) were stirred in DMF (3 ml) for one hour. The reaction was then taken up in ethyl acetate (30 ml) and washed with aqueous K2CO3 (10%), water, and brine. The organic phase was dried (MgSO4) and evaporated to give an orange oil. Chromatography of the residue over silica with a gradient of hexane to 100% ethyl acetate gave (R)-(4,4-difluorocyclohexyl)(3-methyl-4-(1-phenylpyrido[3,4-d]pyridazin-4-yl)piperazin-1-yl)methanone 17 as a yellow solid. LC/MS m/z=452 (M+H+).

後処理

  1. washwashed with aqueous K2CO3 (10%), water, and brine
  2. dry with materialThe organic phase was dried (MgSO4)
  3. customevaporated
  4. customto give an orange oil

出典と根拠

ORDレコード
ord-b3d779c93b384f2e904585bed1589a9a
出典データセット
uspto-grants-2012_07
特許番号
US08222251B2

反応ノート

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