Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → tert-butyl 2-(4-(2-(2,5-dimethoxyphenyl)acetamido)-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate

HRID 923609

反応式

HRID 923609 の反応式
[NH2:1][C:2]1[CH:43]=[CH:42][C:5]([C:6]([N:8]([CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([C:27]5[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=5)=[CH:23][CH:22]=4)[N:17]=3)=[CH:12][CH:11]=2)=[O:7])=[CH:4][CH:3]=1.CO[C:46]1[CH:51]=[CH:50][CH:49]=[C:48]([O:52][CH3:53])[C:47]=1[CH2:54][C:55]([OH:57])=O.CN([C:61]([O:65]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CN(C1C=CN=CC=1)C.CC(=O)OCC>[CH3:53][O:52][C:48]1[CH:49]=[CH:50][C:51]([O:65][CH3:61])=[CH:46][C:47]=1[CH2:54][C:55]([NH:1][C:2]1[CH:43]=[CH:42][C:5]([C:6]([N:8]([CH2:34][C:35]([O:37][C:38]([CH3:39])([CH3:40])[CH3:41])=[O:36])[CH2:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([C:27]5[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=5)=[CH:23][CH:22]=4)[N:17]=3)=[CH:14][CH:15]=2)=[O:7])=[CH:4][CH:3]=1)=[O:57]

参加物

7

反応物 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)3 回HCID 189315722-(2,6-Dimethoxyphenyl)acetic acid2 回HCID 89284665tert-butyl 2-(4-amino-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate

生成物 1

HCID 71111955tert-butyl 2-(4-(2-(2,5-dimethoxyphenyl)acetamido)-N-(4-(3-(4'-methyl-[1,1'-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate収率 40%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Prepared using General Procedure 6. To a suspension of tert-butyl 2-(4-amino-N-(4-(3-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate INT-64 (90 mg, 0.157 mmol) and 2-(2,6-dimethoxyphenyl)acetic acid (30.7 mg, 0.157 mmol) stirring in DMF (2 mL) were added HATU (65.5 mg, 0.172 mmol), DMAP (15 mg, 0.123 mmol) and TEA (54.6 μL, 0.392 mmol). After stirring at room temperature for 18 h 2-(2,6-dimethoxyphenyl)acetic acid (30.7 mg, 0.157 mmol), HATU (65.5 mg, 0.172 mmol) and TEA (21.83 μl, 0.157 mmol) were added. The reaction mixture was stirred at room temperature for 72 h then at 50° C. for 2 h and 60° C. for 2 h. The reaction mixture was cooled to room temperature and more HATU (65.5 mg, 0.172 mmol) was added. After 18 h the reaction mixture was diluted with EA (25 mL) and washed with NaHCO3 (2×25 mL), 1 M HCl (2×25 mL) and brine (25 mL). The combined organics were dried over MgSO4 and concentrated in vacuo. The crude product was purified by chromatography (EA/hexanes) to afford 47 mg (40%) of tert-butyl 2-(4-(2-(2,5-dimethoxyphenyl)acetamido)-N-(4-(3-(4′-methyl-[1,1′-biphenyl]-4-yl)-1,2,4-oxadiazol-5-yl)benzyl)benzamido)acetate INT-66. LCMS-ESI (m/z) calculated for C45H44N4O7: 752; found 753 [M+H]+, tR=2.79 min (Method 10).

後処理

  1. customPrepared
  2. additionwere added
  3. waitat 50° C. for 2 h
  4. wait60° C. for 2 h
  5. temperatureThe reaction mixture was cooled to room temperature
  6. washwashed with NaHCO3 (2×25 mL), 1 M HCl (2×25 mL) and brine (25 mL)
  7. dry with materialThe combined organics were dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by chromatography (EA/hexanes)

出典と根拠

ORDレコード
ord-3517a46bff9a41788825ff7c3b0aba9c
出典データセット
uspto-grants-2016_03
特許番号
US09278910B2

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