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Acetic Acid → tert-butyl[2-(4-{[3-carbamoyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazolin-1-yl]methyl}piperidin-1-yl)ethyl]carbamate

HRID 45802
ノート
印刷プレビュー

反応式

HRID 45802 の反応式
[CH3:1][S:2][C:3]1[N:12]=[CH:11][C:10]2[CH:9]=[CH:8][C:7]3[C:13]([C:23]([NH2:25])=[O:24])=[N:14][N:15]([CH2:16][CH:17]4[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]4)[C:6]=3[C:5]=2[N:4]=1.C(O)(=O)C.O=[CH:31][CH2:32][NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37].[BH3-]C#N.[Na+]>CO.CN(C=O)C>[C:36]([O:35][C:34](=[O:40])[NH:33][CH2:32][CH2:31][N:20]1[CH2:21][CH2:22][CH:17]([CH2:16][N:15]2[C:6]3[C:5]4[N:4]=[C:3]([S:2][CH3:1])[N:12]=[CH:11][C:10]=4[CH:9]=[CH:8][C:7]=3[C:13]([C:23](=[O:24])[NH2:25])=[N:14]2)[CH2:18][CH2:19]1)([CH3:39])([CH3:38])[CH3:37]
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 176Acetic AcidHCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 5003444Sodium cyanoborohydrideHCID 573895548-(methylsulfanyl)-1-(piperidin-4-ylmethyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

生成物 1

HCID 68171502tert-butyl[2-(4-{[3-carbamoyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazolin-1-yl]methyl}piperidin-1-yl)ethyl]carbamate収率 75%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 8-(methylsulfanyl)-1-(piperidin-4-ylmethyl)-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide 26 mg (0.073 mmol) in methanol (1.5 ml) and DMF (1 ml), acetic acid 13 μl (0.219 mmol), tert-butyl (2-oxoethyl)carbamate 69.6 mg (0.438 mmol) and NaCNBH3 28 mg (0.438 mmol) were added. The mixture was stirred at r.t. for 18 hours, consequently the volatiles were removed in vacuo. The residue was dissolved with ethyl acetate and portioned with water; the organic layer was washed with brine, dried over Na2SO4 and concentrated. The crude was purified by flash chromatography (DCM/MeOH 95/5) to give tert-butyl[2-(4-{[3-carbamoyl-8-(methylsulfanyl)-1H-pyrazolo[4,3-h]quinazolin-1-yl]methyl}piperidin-1-yl)ethyl]carbamate 27 mg as a white solid (75%). LC/MS (254) HPLC method 2 Rt 3.86 min. 1H NMR (401 MHz, DMSO-d6) δ 9.47 (s, 1H), 8.28 (d, J=8.67 Hz, 1H), 7.81 (s, 1H), 7.74 (d, J=8.79 Hz, 1H), 7.54 (br. s., 1H), 6.56 (br. s., 1H), 5.08 (d, J=7.32 Hz, 2H), 2.93-3.05 (m, 2H), 2.76-2.84 (m, J=10.25 Hz, 2H), 2.71 (s, 3H), 2.27 (br. s., 1H), 2.14 (br. s., 1H), 1.75-1.94 (m, 2H), 1.12-1.49 (m, 17H). HRMS (ESI) calcd for C24H33N7O3S [M+H]+ 500.2439 found 500.2436.

後処理

  1. customconsequently the volatiles were removed in vacuo
  2. dissolutionThe residue was dissolved with ethyl acetate
  3. washthe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude was purified by flash chromatography (DCM/MeOH 95/5)

出典と根拠

ORDレコード
ord-40ed8d2a2420424f8d044ea37cc2b8b8
出典データセット
uspto-grants-2013_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08541576B2

反応ノート

読み込み中…

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