Water → HCID 86684376, compound

HRID 1411791Notes

Reaction equation

HRID 1411791 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:37]2[CH2:49][CH2:48][N:40]3[C:41]4[CH2:42][CH2:43][CH2:44][CH2:45][C:46]=4[CH:47]=[C:39]3[C:38]2=[O:50])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH2:26][CH2:27][N:28]([CH:31]4[CH2:34][O:33][CH2:32]4)[CH2:29][CH:30]=3)=[CH:21][N:20]=2)[C:15](=[O:35])[N:14]([CH3:36])[CH:13]=1)(=O)C.[OH-].[Li+].O>C1COCC1.C(O)(C)C>[OH:4][CH2:5][C:6]1[C:7]([N:37]2[CH2:49][CH2:48][N:40]3[C:41]4[CH2:42][CH2:43][CH2:44][CH2:45][C:46]=4[CH:47]=[C:39]3[C:38]2=[O:50])=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH2:26][CH2:27][N:28]([CH:31]4[CH2:32][O:33][CH2:34]4)[CH2:29][CH:30]=3)=[CH:21][N:20]=2)[C:15](=[O:35])[N:14]([CH3:36])[CH:13]=1

Participants

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 86684375HCID 86684375, compound

Product 1

HCID 86684376HCID 86684376, compoundYield 21.5%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 200f (260 mg, 0.39 mmol) and lithium hydroxide (92.4 mg, 3.85 mmol) in THF (9 mL), isopropanol (6 mL), and water (1 mL) was stirred at room temperature for 0.5 h. The mixture was extracted concentrated under reduced pressure and diluted with water (4 mL). It was then extracted with dichloromethane (2×10 mL) and the combined C dichloromethane extract was concentrated under reduced pressure. The residue was purified with reverse-phase prep-HPLC to afford 200 (53.1 mg, 20%) as yellow solid. MS-ESI: [M+H]+ 634.2. 1H NMR (500 MHz, DMSO-d6) δ 8.76 (d, J=1.5 Hz, 1H), 8.74 (s, 1H), 8.49 (d, J=5.5 Hz, 1H), 8.24 (d, J=2.0 Hz, 1H), 7.73-7.71 (m, 1H), 7.54 (d, J=2.5 Hz, 1H), 7.36 (d, J=5.0 Hz, 1H), 7.30 (d, J=8.5 Hz, 1H), 6.58 (s, 1H), 6.11 (s, 1H), 4.97 (s, 1H), 4.57 (t, J=6.5 Hz, 2H), 4.38-4.49 (m, 4H), 4.08-4.26 (m, 3H), 3.86 (d, J=12.0 Hz, 1H), 3.61 (s, 3H), 3.54-3.45 (m, 1H), 2.95 (s, 2H), 2.68-2.54 (m, 2H), 2.48-2.46 (m, overlap, 6H),1.83-1.75 (m, 2H), 1.73-1.65 (m, 2H).

Workup

  1. extractionThe mixture was extracted
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with water (4 mL)
  4. extractionIt was then extracted with dichloromethane (2×10 mL)
  5. extractionthe combined C dichloromethane extract
  6. concentrationwas concentrated under reduced pressure
  7. customThe residue was purified with reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-7163083cd2b94fdcb18c5f35e0511468
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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