Triethylamine → N1-(2-(2-hydroxyethoxy)ethyl)-N3-(4-(piperidin-1-yl)-2-(6-((3-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)phenyl)isophthalamide

HRID 1408121ノート

反応式

HRID 1408121 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[C:14]1[N:19]=[CH:18][N:17]=[C:16]([NH:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)[CH:15]=1.[OH:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][NH:38][C:39]([C:41]1[CH:42]=[C:43]([CH:47]=[CH:48][CH:49]=1)[C:44](O)=[O:45])=[O:40].C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CN(C)C=O>[OH:32][CH2:33][CH2:34][O:35][CH2:36][CH2:37][NH:38][C:39](=[O:40])[C:41]1[CH:49]=[CH:48][CH:47]=[C:43]([C:44]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]3)=[CH:4][C:3]=2[C:14]2[CH:15]=[C:16]([NH:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:30])([F:29])[F:31])[CH:23]=3)[N:17]=[CH:18][N:19]=2)=[O:45])[CH:42]=1

参加物

7

反応物 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665867546-(2-amino-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)-pyrimidin-4-amineHCID 665867923-((2-(2-Hydroxyethoxy)ethyl)carbamoyl)benzoic acid

生成物 1

HCID 86705958N1-(2-(2-hydroxyethoxy)ethyl)-N3-(4-(piperidin-1-yl)-2-(6-((3-(trifluoromethyl)benzyl)amino)pyrimidin-4-yl)phenyl)isophthalamide収率 18%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Into a 100-mL round bottom flask, was placed a solution of 6-(2-amino-5-(piperidin-1-yl)phenyl)-N-(3-(trifluoromethyl)benzyl)pyrimidin-4-amine (300 mg, 0.70 mmol, 1.00 equiv) in N,N-dimethylformamide (6 mL). This was followed by the addition of 3-(2-(2-hydroxyethoxy)ethylcarbamoyl)benzoic acid (302.2 mg, 1.19 mmol, 1.70 equiv) at room temperature. To this was added triethylamine (156 mg, 1.54 mmol, 2.20 equiv). To the mixture was added EDC.HCl (148.2 mg, 0.78 mmol, 1.10 equiv) at room temperature, followed by HOBT (104.4 mg, 0.77 mmol, 1.10 equiv) at room temperature. The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. The crude product was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 83.6 mg (15%) of a yellow solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 8.76 (s, 1H), 8.40 (s, 1H), 8.039 (t, J=8.1 Hz, 2H), 7.74 (s, 1H), 7.63˜7.57 (m, 3H), 7.53˜7.50 (m, 2H), 7.47˜7.40 (m, 2H), 6.93 (s, 1H), 4.81 (s, 2H), 3.71˜3.58 (m, 8H), 3.43˜3.39 (m, 4H), 1.84˜1.81 (m, 6H). MS (ES, m/z): 663 [M+H]+.

後処理

  1. customInto a 100-mL round bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. customThe crude product was purified by reverse phase HPLC
  4. washeluting with a water/CH3CN gradient
  5. additioncontaining 0.05% TFA

出典と根拠

ORDレコード
ord-268544cc837046a095e0e6cd5097091f
出典データセット
uspto-grants-2014_12
特許番号
US08916569B2

反応ノート

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