Hydrochloric Acid → 3-({5-[3-Methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid

HRID 1427499ノート

反応式

HRID 1427499 の反応式
C([O:3][C:4](=[O:38])[CH2:5][CH2:6][NH:7][C:8]([C:10]1[N:15]=[CH:14][C:13]([NH:16][CH:17]([C:22]2[CH:27]=[CH:26][C:25]([C:28]3[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=3)=[CH:24][CH:23]=2)[CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:12][N:11]=1)=[O:9])C.FC(F)(F)C1C=CC(C2N=CC(NC(C3C=CC(C(NCCC(O)=O)=O)=CC=3)CCC)=CN=2)=CC=1.[OH-].[Na+].Cl>O1CCCC1.CO>[CH3:20][CH:19]([CH3:21])[CH2:18][CH:17]([NH:16][C:13]1[CH:12]=[N:11][C:10]([C:8]([NH:7][CH2:6][CH2:5][C:4]([OH:38])=[O:3])=[O:9])=[N:15][CH:14]=1)[C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:29]=[CH:30][C:31]([C:34]([F:36])([F:35])[F:37])=[CH:32][CH:33]=2)=[CH:24][CH:23]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 679806583-({5-[3-Methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid ethyl esterHCID 679808383-(4-(1-(2-(4-(Trifluoromethyl)phenyl)pyrimidin-5-ylamino)butyl)benzamido)propanoic acid

生成物 1

HCID 573888553-({5-[3-Methyl-1-(4'-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid収率 78%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

3-({5-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid ethyl ester Peak 2 (150 mg, 0.284 mmol) was dissolved in tetrahydrofuran (3 mL) and methanol (1 mL), and 1.0 M NaOH (1 mL) was added. This was stirred at room temperature for 10 min. The reaction brought to pH 4 with 1 N HCl. This was extracted twice with ethyl acetate. The combined organics were dried over MgSO4 and concentrated in vacuo to give an oil. The material was triturated with four portions of diethylether to give the opposite enantiomer of 3-({5-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid (111 mg, 78%) as a white solid. 1H NMR (400 MHz, DMSO-d6, δ): 12.21 (br. s., 1H) 8.39 (t, J=6.0 Hz, 1H) 8.16 (s, 2H) 7.83-7.91 (m, 2H) 7.75-7.81 (m, 2H) 7.70 (d, J=8.2 Hz, 2H) 7.54 (d, J=8.2 Hz, 2H) 7.27 (d, J=7.6 Hz, 1H) 4.61-4.72 (m, 1H) 3.36-3.45 (m, 2H) 2.44 (t, J=6.9 Hz, 2H) 1.74-1.85 (m, 1H) 1.62-1.72 (m, 1H) 1.50-1.61 (m, 1H) 0.98 (d, J=6.4 Hz, 3H) 0.92 (d, J=6.4 Hz, 3H); MS (M+1): 501.6.

後処理

  1. extractionThis was extracted twice with ethyl acetate
  2. dry with materialThe combined organics were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customto give an oil
  5. customThe material was triturated with four portions of diethylether

出典と根拠

ORDレコード
ord-e766f815b38f4ddead985f815cf7c5a9
出典データセット
uspto-grants-2015_01
特許番号
US08933104B2

反応ノート

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