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

HRID 1427498ノート

反応式

HRID 1427498 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 97%

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 1 (286.4 mg, 0.542 mmol) was dissolved in tetrahydrofuran (3 mL) and methanol (1 mL), and 1.0 M NaOH (2 mL, 2 mmol) was added. This was stirred at room temperature for 10 min. The reaction brought to pH 3 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 one enantiomer of 3-({5-[3-methyl-1-(4′-trifluoromethyl-biphenyl-4-yl)-butylamino]-pyrimidine-2-carbonyl}-amino)-propionic acid (266 mg, 97%) 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) 4.60-4.72 (m, 1H) 3.36-3.46 (m, 2H) 2.44 (t, J=6.9 Hz, 2H) 1.74-1.85 (m, 1H) 1.67 (m, 1H) 1.51-1.60 (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-9dd7071628d64a1d9524036f85f6346f
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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