Water → HCID 71526522, compound

HRID 1026406Notes

Reaction equation

HRID 1026406 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])=[CH:10][C:9]([F:26])=[CH:8][C:7]=1[C:27]1[CH:32]=[C:31]([NH:33][C:34]2[CH:39]=[CH:38][C:37]([N:40]3[CH2:45][CH2:44][N:43]([CH:46]4[CH2:49][O:48][CH2:47]4)[CH2:42][C@@H:41]3[CH3:50])=[CH:36][N:35]=2)[C:30](=[O:51])[N:29]([CH3:52])[CH:28]=1)(=O)C.O.[Li+].[OH-]>C1COCC1>[F:26][C:9]1[CH:8]=[C:7]([C:27]2[CH:32]=[C:31]([NH:33][C:34]3[CH:39]=[CH:38][C:37]([N:40]4[CH2:45][CH2:44][N:43]([CH:46]5[CH2:47][O:48][CH2:49]5)[CH2:42][C@@H:41]4[CH3:50])=[CH:36][N:35]=3)[C:30](=[O:51])[N:29]([CH3:52])[CH:28]=2)[C:6]([CH2:5][OH:4])=[C:11]([N:12]2[CH2:24][CH2:23][N:15]3[C:16]4[CH2:17][CH2:18][CH2:19][CH2:20][C:21]=4[CH:22]=[C:14]3[C:13]2=[O:25])[CH:10]=1

Participants

5

Reactant 3

HCID 962Water2×HCID 3939Lithium HydroxideHCID 86683709HCID 86683709, compound

Product 1

HCID 71526522HCID 71526522, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

At room temperature, to a solution of 106a (153 mg 0.22 mmol) in THF/iPA/H2O (6 mL/6 mL/2 mL) was added LiOH (70 mg, 2.9 mmol) while stirring. This mixture was stirred for 0.5 h. Then, H2O (20 mL) was added and the mixture was extracted with EA (30 mL×3). The combined organic layer was dried with Na2SO4 and concentrated to give a yellow solid, which was further purified by reverse-phase prep-HPLC to afford 106 as a white solid (60 mg, 42% yield). LCMS: [M+H]+ 668. 1H NMR (500 MHz, CDCl3) δ 8.57 (dd, J=2.0, 7.0, 1H), 7.97 (s, 1H), 7.85 (s, 1H), 7.48 (t, J=2.5, 1H), 7.33 (d, J=7.0, 1H), 7.16 (d, J=8.0, 1H), 6.96 (dd, J=2.5, 9.0, 1H), 6.87 (s, 1H), 6.83 (d, J=9.0, 1H), 4.69-4.72 (m, 4H), 4.55 (d, J=11.5, 1H), 4.29-4.38 (m, 2H), 4.14-4.20 (m, 3H), 3.90-3.93 (m, 1H), 3.71 (s, 3H), 3.57 (s, 1H), 3.48 (s, 1H), 3.09-3.14 (m, 2H), 2.52-2.61 (m, 7H), 2.23 (s, 1H), 1.88-1.91 (m, 2H), 1.79-1.81 (m, 2H), 0.99 (d, J=5.0, 3H)

Workup

  1. stirringThis mixture was stirred for 0.5 h
  2. extractionthe mixture was extracted with EA (30 mL×3)
  3. dry with materialThe combined organic layer was dried with Na2SO4
  4. concentrationconcentrated
  5. customto give a yellow solid, which
  6. customwas further purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-f9bab20861b648668bf8f5b8e7d9ec8e
Source dataset
uspto-grants-2014_05
Patent number
US08729072B2

Reaction notes

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