Diisopropylethylamine → N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-{[3-(1-piperidinyl)propanoyl]amino}-1H-indole-2-carboxamide trifluoroacetate

HRID 1875019ノート

反応式

HRID 1875019 の反応式
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[Cl-].[F:29][C:30]([F:35])([F:34])[C:31]([OH:33])=[O:32].[NH2:36][C:37]1[CH:38]=[C:39]2[C:43](=[CH:44][CH:45]=1)[NH:42][C:41]([C:46]([NH:48][CH2:49][C:50]1[CH:55]=[CH:54][C:53]([Cl:56])=[C:52]([O:57][C:58]3[CH:63]=[C:62]([C:64]#[N:65])[CH:61]=[C:60]([Cl:66])[CH:59]=3)[C:51]=1[F:67])=[O:47])=[CH:40]2.[N:68]1([CH2:74][CH2:75][C:76](O)=[O:77])[CH2:73][CH2:72][CH2:71][CH2:70][CH2:69]1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[F:29][C:30]([F:35])([F:34])[C:31]([OH:33])=[O:32].[Cl:56][C:53]1[CH:54]=[CH:55][C:50]([CH2:49][NH:48][C:46]([C:41]2[NH:42][C:43]3[C:39]([CH:40]=2)=[CH:38][C:37]([NH:36][C:76](=[O:77])[CH2:75][CH2:74][N:68]2[CH2:73][CH2:72][CH2:71][CH2:70][CH2:69]2)=[CH:45][CH:44]=3)=[O:47])=[C:51]([F:67])[C:52]=1[O:57][C:58]1[CH:63]=[C:62]([C:64]#[N:65])[CH:61]=[C:60]([Cl:66])[CH:59]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 1177821-Piperidinepropanoic acidHCID 866448845-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetateHCID 131720136BOP chloride

生成物 1

HCID 86644906N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-{[3-(1-piperidinyl)propanoyl]amino}-1H-indole-2-carboxamide trifluoroacetate収率 43%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

BOP chloride (0.079 g, 0.309 mmol) was added to a solution of 5-amino-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-indole-2-carboxamide trifluoroacetate (0.060 g, 0.103 mmol), 3-(1-piperidinyl)propanoic acid (0.0162 g, 0.103 mmol) and diisopropylethylamine (0.090 mL, 0.514 mmol) in DMF (1 mL). The mixture was stirred at room temperature for 1 hr. The reaction mixture was extracted with ethyl acetate and water. The organic layer was washed with water, dried over sodium sulfate and concentrated. The residue was purified by reverse phase HPLC (acetonitrile:water with 0.% trifluoroacetic acid) to give 0.032 g (43%) of the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.56 (br. s., 1H), 10.01 (br. s., 1H), 9.01-9.18 (m, 1H), 8.97 (d, 1H), 7.92 (br. s., 1H), 7.68-7.84 (m, 1H), 7.40-7.56 (m, 2H), 7.27-7.41 (m, 2H), 7.15-7.28 (m, 1H), 7.08 (s, 1H), 4.36-4.68 (m, 2H), 3.22-3.48 (m, 4H), 2.67-2.98 (m, 4H), 1.72-1.87 (m, 2H), 1.48-1.71 (m, 3H), 1.20-1.43 (m, 1H). ES MS: m/z 608 (M+1).

後処理

  1. extractionThe reaction mixture was extracted with ethyl acetate and water
  2. washThe organic layer was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase HPLC (acetonitrile:water with 0.% trifluoroacetic acid)

出典と根拠

ORDレコード
ord-e37c9da98a7d4b1c9fb9aaa0e39153e8
出典データセット
uspto-grants-2012_11
特許番号
US08304419B2

反応ノート

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