Diisopropylethylamine → (2S,4S)-1-(2-(2H-1,2,3-triazol-2-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-(thien-2-ylmethyl)pyrrolidine-2-carboxamide

HRID 1630277ノート

反応式

HRID 1630277 の反応式
[F:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C@@H:16]3[CH2:20][C@@H:19]([CH2:21][C:22]4[S:23][CH:24]=[CH:25][CH:26]=4)[CH2:18][NH:17]3)=[O:15])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[N:29]1[N:30]([CH2:34][C:35](O)=[O:36])[N:31]=[CH:32][CH:33]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[N:29]1[N:30]([CH2:34][C:35]([N:17]2[CH2:18][C@H:19]([CH2:21][C:22]3[S:23][CH:24]=[CH:25][CH:26]=3)[CH2:20][C@H:16]2[C:14]([NH:13][C:10]2[CH:9]=[CH:8][C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:28][CH:27]=3)=[CH:12][CH:11]=2)=[O:15])=[O:36])[N:31]=[CH:32][CH:33]=1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 234341642-(2H-1,2,3-triazol-2-yl)acetic acidHCID 46901321HCID 46901321、化合物

生成物 1

HCID 45377438(2S,4S)-1-(2-(2H-1,2,3-triazol-2-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-(thien-2-ylmethyl)pyrrolidine-2-carboxamide収率 6%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A flask was charged with (2S,4S)—N-(4-(4-fluorophenoxy)phenyl)-4-(thien-2-ylmethyl)pyrrolidine-2-carboxamide (84 mg, 0.21 mmol), 2-(2H-1,2,3-triazol-2-yl)acetic acid (29 mg, 0.23 mmol), DIEA (0.5 mL, 2.9 mmol), HATU (81 mg, 0.21 mmol) and DMF (3 mL). The reaction mixture was stirred at ambient temperature for 20 minutes and quenched with saturated sodium bicarbonate (aq., 10 mL). The mixture was extracted with ethyl acetate (20 mL) and the extract was washed with deionized water (10 mL) and then brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by reverse phase HPLC to give Compound 64, (2S,4S)-1-(2-(2H-1,2,3-triazol-2-yl)acetyl)-N-(4-(4-fluorophenoxy)phenyl)-4-(thien-2-ylmethyl)pyrrolidine-2-carboxamide (6.1 mg, 0.012 mmol, 6% yield), as an off-white solid. 1H-NMR (400 MHz, CDCl3): 9.15 (s, 1H), 7.72 (s, 2H), 7.44 (d, J=8.8 Hz, 2H), 7.18-7.16 (m, 1H), 7.03-6.82 (m, 8H), 5.29 (s, 2H), 4.86 (d, J=8.0 Hz), 3.63-3.58 (m, 1H), 3.25-3.20 (m, 1H), 3.12 (dd, J=13.6, 4.8 Hz, 1H), 3.01-2.87 (m, 2H), 2.73 (dd, J=12.4, 5.2 Hz, 1H), 1.75-1.68 (m, 1H). MS (EI) for C26H24FN5O3S. found 506.2 (MH+).

後処理

  1. customquenched with saturated sodium bicarbonate (aq., 10 mL)
  2. extractionThe mixture was extracted with ethyl acetate (20 mL)
  3. washthe extract was washed with deionized water (10 mL)
  4. dry with materialbrine (10 mL), dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customProduct was purified from the residue by reverse phase HPLC

出典と根拠

ORDレコード
ord-fbc8e3402c2141c29ead9efc795b02cb
出典データセット
uspto-grants-2014_07
特許番号
US08791102B2

反応ノート

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