Hydrazine → N-[(1S)-2-amino-1-(cyclohexylmethyl)ethyl]-4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-chloro-2-thiophenecarboxamide

HRID 1845475ノート

反応式

HRID 1845475 の反応式
[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH3:36])[C:6]=1[C:7]1[CH:8]=[C:9]([C:13]([NH:15][C@H:16]([CH2:24][N:25]2C(=O)C3C(=CC=CC=3)C2=O)[CH2:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:14])[S:10][C:11]=1[Cl:12].NN>O1CCCC1.CO>[NH2:25][CH2:24][C@@H:16]([NH:15][C:13]([C:9]1[S:10][C:11]([Cl:12])=[C:7]([C:6]2[N:5]([CH3:36])[N:4]=[CH:3][C:2]=2[Br:1])[CH:8]=1)=[O:14])[CH2:17][CH:18]1[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1

参加物

5

反応物 2

HCID 9321HydrazineHCID 578268544-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-chloro-N-{(1S)-2-cyclohexyl-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}-2-thiophenecarboxamide

生成物 1

HCID 24996917N-[(1S)-2-amino-1-(cyclohexylmethyl)ethyl]-4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-chloro-2-thiophenecarboxamide収率 25%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-chloro-N-{(1S)-2-cyclohexyl-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]ethyl}-2-thiophenecarboxamide (48 mg, 0.08 mmol) in tetrahydrofuran (0.41 ml) and methanol (0.41 ml) at 25° C. was added hydrazine (0.03 ml, 0.81 mmol) dropwise. After 12 h, the solution was concentrated, dry loaded onto silica and purified by column chromatography (5% MeOH in DCM (1% NH4OH)). The free base was then converted to the HCl salt by adding excess 4M HCl in dioxane (1 ml) to the residue in MeOH (2 ml) affording the HCl salt of N-[(1S)-2-amino-1-(cyclohexylmethyl)ethyl]-4-(4-bromo-1-methyl-1H-pyrazol-5-yl)-5-chloro-2-thiophenecarboxamide (11 mg, 0.02 mmol, 24% yield) as a yellow solid: LCMS (ES) m/z=459, 461 (M, M+2)+, 1H NMR (400 MHz, DMSO-d6) δ ppm 8.73 (br. s., 1H) 7.96 (br. s., 4H) 7.74 (s, 1H) 4.21-4.26 (m, 1H) 3.77 (s, 3H) 2.92-2.99 (m, 2H) 1.73-1.79 (m, 1H) 1.62-1.67 (m, 4H) 1.49-1.51 (m, 1H) 1.25 (br. s., 2H) 1.06-1.13 (m, 2H) 0.95 (d, J=6.82 Hz, 1H) 0.82-0.89 (m, 1H).

後処理

  1. concentrationthe solution was concentrated
  2. customdry loaded onto silica
  3. custompurified by column chromatography (5% MeOH in DCM (1% NH4OH))
  4. additionby adding excess 4M HCl in dioxane (1 ml) to the residue in MeOH (2 ml)

出典と根拠

ORDレコード
ord-fda4b7364e85448ab4566bb3ea77b02f
出典データセット
uspto-grants-2015_02
特許番号
US08946278B2

反応ノート

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