1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(2-(2-(2-((2-Methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 705778ノート

反応式

HRID 705778 の反応式
[CH3:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[CH:5]=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:30][C:31]([O:33]C)=O)[C:19]([C:35]([F:38])([F:37])[F:36])=[CH:18][N:17]=1.O[Li].O.C1C=CC2N(O)N=[N:48]C=2C=1.CCN=C=NCCCN(C)C.C(=O)([O-])[O-].[NH4+].[NH4+].CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C.CO.O>[CH3:1][C:2]1[CH:7]=[C:6]([CH:8]2[CH2:9][CH2:10][N:11]([CH3:14])[CH2:12][CH2:13]2)[CH:5]=[CH:4][C:3]=1[NH:15][C:16]1[N:21]=[C:20]([CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:30][C:31]([NH2:48])=[O:33])[C:19]([C:35]([F:36])([F:37])[F:38])=[CH:18][N:17]=1

参加物

11

反応物 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 168937Lithium hydroxide, monohydrateHCID 517111Ammonium CarbonateHCID 68282776Methyl 2-(2-(2-(2-((2-methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

生成物 1

HCID 601622502-(2-(2-(2-((2-Methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide収率 77.2%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Methyl 2-(2-(2-(2-((2-methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate (I55) (476 mg, 0.906 mmol) and LiOH.H2O (113 mg, 2.71 mmol) in a mixture of THF (20 mL), water (4 mL) and MeOH (2 mL) were stirred at room temperature for 24 hours. The volatiles were evaporated under reduced pressure to give a light yellow solid which was dissolved in dry DMF (10 mL) and dry THF (10 mL), HOBT (171 mg, 1.26 mmol), EDCI (196 mg, 1.26 mmol), ammonium carbonate (458 mg, 4.87 mmol) and DIPEA (829 μL, 4.87 mmol) were added and the resulting mixture was stirred at room temperature for 16 hours. The volatiles were evaporated under reduced pressure and the residue taken up in ethyl acetate. The resulting solution was washed with 10% NaHCO3, the layers separated and the organic layer was dried (MgSO4). The volatiles were evaporated under reduced pressure and the residue chromatographed (SiO2, 0-100% MeOH/DCM) to give the title compound (12) (358 mg, 52%) as a cream solid; 1H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.58 (d, J=89 Hz, 1H), 7.34 (s, 1H), 7.28-7.19 (m, 4H), 7.14-7.09 (m, 2H), 5.66 (s, 1H), 5.49 (s, 1H), 3.65 (s, 2H), 3.13-3.04 (m, 4H), 3.04-2.97 (m, 2H), 2.54-2.41 (m, 1H), 2.35 (s, 3H), 2.30 (s, 3H), 2.08 (td, J=11.3, 3.8 Hz, 2H), 1.88-1.80 (m, 4H). LCMS Method C: rt 4.91 min; m/z 512.2 [M+1]+, 510.2 [M−1]−.

後処理

  1. customThe volatiles were evaporated under reduced pressure
  2. customto give a light yellow solid which
  3. stirringthe resulting mixture was stirred at room temperature for 16 hours
  4. customThe volatiles were evaporated under reduced pressure
  5. washThe resulting solution was washed with 10% NaHCO3
  6. customthe layers separated
  7. dry with materialthe organic layer was dried (MgSO4)
  8. customThe volatiles were evaporated under reduced pressure
  9. customthe residue chromatographed (SiO2, 0-100% MeOH/DCM)

出典と根拠

ORDレコード
ord-0d2f902b07874c96b0cd2a1da3150f25
出典データセット
uspto-grants-2015_11
特許番号
US09174946B2

反応ノート

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