1-Hydroxybenzotriazole → 2-(2-(2-(2-((2-Methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 2272444노트

반응식

HRID 2272444 반응식
[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.Cl.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

참가 물질

11

반응물 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 168937Lithium hydroxide, monohydrateHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68282776Methyl 2-(2-(2-(2-((2-methyl-4-(1-methylpiperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetate

생성물 1

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

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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), EDCl (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=8.9 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]−.

후처리

  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)

출처 및 근거

ORD 기록
ord-3b40ad8430c84b248d419b9fa60c608b
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09120761B2

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