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Diisopropylethylamine → N-[((1S,4S,6S)-3-{[6-Methyl-3-(2-pyrimidinyl)-2-pyridinyl]carbonyl}-3-azabicyclo[4.1.0]hept-4-yl)methyl]-5-(trifluoromethyl)-2-pyridinamine

HRID 1094778
ノート
印刷プレビュー

反応式

HRID 1094778 の反応式
[CH3:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])=O)[C:5]([C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.[C@H:26]12[CH2:32][C@H:31]1[CH2:30][C@@H:29]([CH2:33][NH:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]([F:44])([F:43])[F:42])=[CH:37][N:36]=1)[NH:28][CH2:27]2.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][C:2]1[N:7]=[C:6]([C:8]([N:28]2[C@H:29]([CH2:33][NH:34][C:35]3[CH:40]=[CH:39][C:38]([C:41]([F:42])([F:43])[F:44])=[CH:37][N:36]=3)[CH2:30][C@H:31]3[C@H:26]([CH2:32]3)[CH2:27]2)=[O:10])[C:5]([C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)=[CH:4][CH:3]=1
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 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584779466-Methyl-3-(2-pyrimidinyl)-2-pyridinecarboxylic acidHCID 59396026N-[(1S,4S,6S)-3-Azabicyclo[4.1.0]hept-4-ylmethyl]-5-(trifluoromethyl)-2-pyridinamine

生成物 1

HCID 46222789
N-[((1S,4S,6S)-3-{[6-Methyl-3-(2-pyrimidinyl)-2-pyridinyl]carbonyl}-3-azabicyclo[4.1.0]hept-4-yl)methyl]-5-(trifluoromethyl)-2-pyridinamine

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 6-methyl-3-(2-pyrimidinyl)-2-pyridinecarboxylic acid D19 (99 mg), DIPEA (0.066 ml, 0.376 mmol) and N-[(1S,4S,6S)-3-azabicyclo[4.1.0]hept-4-ylmethyl]-5-(trifluoromethyl)-2-pyridinamine D12 (34 mg) in DCM (3 ml), stirred under nitrogen at room temperature was added TBTU (60.4 mg, 0.188 mmol) in one charge. The reaction mixture was stirred at room temperature for 5 hours. NaHCO3 aqueous saturated solution was added and the aqueous extracted with DCM, the phases were separated on a hydrophobic frit and the combined organic solvent was removed to give the crude product which was purified by flash chromatography (silica —NH 11 g column, gradient elution from Cy to Cy/EtOAc 2:8 in 30 minutes, flow rate 30 mls/minute). The product so obtained was purified a second time by flash chromatography (silica —NH 11 g column gradient elution from Cy to Cy/EtOAc 1:1 in 20 minutes, flow rate 30 mls/minute) to afford the title compound E3 (21 mg). UPLC (Acid GEN_QC): rt1=0.68 minutes, peak observed: 469 (M+1). C24H23F3N6O requires 460. 1H NMR (500 MHz, CDCl3) δ ppm 0.08-0.16 (m, 1 H), 0.73-0.81 (m, 1 H), 0.82-1.32 (m, 3H), 2.46-2.58 (m, 2 H), 2.66 (s, 3 H), 3.52-3.69 (m, 2 H), 3.70-3.80 (m, 1 H), 4.47-4.66 (m, 1 H), 6.38-6.50 (m, 1 H), 6.74-7.01 (m, 1 H), 7.08 (t, 1 H), 7.35 (d, 1 H), 7.47 (d, 1 H), 8.33 (s, 1 H), 8.54-8.64 (m, 3 H).

後処理

  1. additioncharge
  2. extractionthe aqueous extracted with DCM
  3. customthe phases were separated on a hydrophobic frit
  4. customthe combined organic solvent was removed
  5. customto give the crude product which
  6. customwas purified by flash chromatography (silica —NH 11 g column, gradient elution from Cy to Cy/EtOAc 2:8 in 30 minutes, flow rate 30 mls/minute)
  7. customThe product so obtained
  8. customwas purified a second time
  9. washby flash chromatography (silica —NH 11 g column gradient elution from Cy to Cy/EtOAc 1:1 in 20 minutes, flow rate 30 mls/minute)

出典と根拠

ORDレコード
ord-bab9f16ec14d4f9c9febabe903cef971
出典データセット
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08133908B2

反応ノート

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このページの内容参加物実験手順後処理出典と根拠反応ノート