Hydrochloric Acid → HCID 76285608、化合物

HRID 572037ノート

反応式

HRID 572037 の反応式
[CH2:1]([O:8][C@H:9]1[CH2:13][N:12]([C:14]([O:16]C(C)(C)C)=O)[C@H:11]([CH2:21]O)[CH2:10]1)[C:2]1C=CC=CC=1.Cl.O1CCOCC1.[OH:30][CH:31]([C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=1)[C:32]([OH:34])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:56]2[N:57]=[CH:58][CH:59]=[CH:60][C:55]=2[N:54]=N1.C[N:70]1CCO[CH2:72][CH2:71]1>CO>[CH:60]1([C:55]2[N:54]=[CH:2][C:1]([O:8][C@H:9]3[CH2:13][N:12]4[C:14](=[O:16])[CH2:72][CH2:71][N:70]([C:32](=[O:34])[CH:31]([OH:30])[C:35]5[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([F:44])([F:43])[F:42])[CH:36]=5)[CH2:21][C@@H:11]4[CH2:10]3)=[N:57][CH:56]=2)[CH2:59][CH2:58]1

参加物

8

反応物 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 312751,4-DioxaneHCID 101658DL-2-(3-Trifluoromethyl)phenylglycollic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14821719HCID 14821719、化合物

生成物 1

HCID 76285608HCID 76285608、化合物

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

To a solution of the product from Example 28, Part F (90 mg, 0.232 mmol) in anhydrous methanol (3 mL) was added 4 M HCl in 1,4-dioxane (0.579 mL, 2.317 mmol). The resulting mixture was stirred at room temperature for 18 hours, and the volatiles were removed in vacuo. The residue was suspended in N,N-dimethylformamide (3 mL), 2-hydroxy-2-(3-(trifluoromethyl)phenyl)acetic acid (0.056 g, 0.255 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU, 0.106 g, 0.278 mmol), and N-methyl morpholine (0.117 g, 1.158 mmol) were added, and the resulting solution was stirred at room temperature for 16 hours. The mixture was partitioned between water and ethyl acetate. The organic extract was washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-7% methanol in dichloromethane. The title compound was obtained as a colorless solid (0.065 g, 57% yield). 1H NMR (400 MHz, pyridine-d5, 90° C.) δ ppm 8.09-7.99 (m, 2H), 7.98 (d, J=1.4 Hz, 1H), 7.87-7.79 (m, 1H), 7.56 (d, J=1.3 Hz, 1H), 7.43 (t, J=7.8 Hz, 1H), 5.94-5.85 (m, 1H), 5.40 (t, J=4.1 Hz, 1H), 4.90-4.15 (m, 3H), 4.12 (d, J=13.5 Hz, 1H), 3.73 (dd, J=13.5, 4.3 Hz, 1H), 3.50-2.15 (m, 6H), 2.07-1.79 (m, 2H), 1.05-0.93 (m, 2H), 0.95-0.83 (m, 2H).); MS (ESI) m/z 491 (M+H)+.

後処理

  1. customthe volatiles were removed in vacuo
  2. stirringthe resulting solution was stirred at room temperature for 16 hours
  3. customThe mixture was partitioned between water and ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-7% methanol in dichloromethane

出典と根拠

ORDレコード
ord-1a0598faff80408692790122d9cbf55f
出典データセット
uspto-grants-2015_05
特許番号
US09029361B2

反応ノート

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