Lithium Hydroxide → HCID 71526688, compound

HRID 519353Notes

Reaction equation

HRID 519353 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([N:12]2[CH2:23][CH2:22][N:21]3[C:14](=[CH:15][C:16]4[CH2:17][C:18]([CH3:25])([CH3:24])[CH2:19][C:20]=43)[C:13]2=[O:26])=[CH:10][C:9]([F:27])=[CH:8][C:7]=1[C:28]1[CH:33]=[C:32]([NH:34][C:35]2[CH:40]=[CH:39][C:38]([N:41]3[CH2:46][C@@H:45]([CH3:47])[N:44]([CH:48]4[CH2:51][O:50][CH2:49]4)[CH2:43][C@@H:42]3[CH3:52])=[CH:37][N:36]=2)[C:31](=[O:53])[N:30]([CH3:54])[CH:29]=1)(=O)C.[OH-].[Li+]>C(O)(C)C.C1COCC1.O>[CH3:52][C@H:42]1[CH2:43][N:44]([CH:48]2[CH2:51][O:50][CH2:49]2)[C@H:45]([CH3:47])[CH2:46][N:41]1[C:38]1[CH:39]=[CH:40][C:35]([NH:34][C:32]2[C:31](=[O:53])[N:30]([CH3:54])[CH:29]=[C:28]([C:7]3[C:6]([CH2:5][OH:4])=[C:11]([N:12]4[CH2:23][CH2:22][N:21]5[C:20]6[CH2:19][C:18]([CH3:24])([CH3:25])[CH2:17][C:16]=6[CH:15]=[C:14]5[C:13]4=[O:26])[CH:10]=[C:9]([F:27])[CH:8]=3)[CH:33]=2)=[N:36][CH:37]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 89549931HCID 89549931, compound

Product 1

HCID 71526688HCID 71526688, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of 116a (150 mg, 0.20 mmol) and lithium hydroxide (48 mg, 2.0 mmol) in i-propanol/THF (1:1, 4 mL) and water (1 mL) was stirred at 30° C. for 1 h. The mixture was evaporated under reduced pressure. The resulting residue was extracted with ethyl acetate (2×10 mL). The combined organic layer was concentrated under reduced pressure and the residue was purified by reverse-phase prep-HPLC to afford 116 (57 mg, 41%) as white solid. MS: [M+H]+ 696.3. 1H NMR (500 MHz, CDCl3) δ 8.60 (dd, J=2.0, 6.5 Hz, 1H), 8.02 (d, J=2.5 Hz, 1H), 7.88 (s, 1H), 7.50-7.49 (m, 1H), 7.37 (d, J=8.5 Hz, 1H), 7.16 (d, J=9.0 Hz, 1H), 6.96 (dd, J=2.5, 9.0 Hz, 1H), 6.83-6.81 (m, 2H), 4.77-4.74 (m, 2H), 4.66-4.62 (m, 2H), 4.57-4.55 (m, 1H), 4.33-4.31 (m, 1H), 4.23-4.14 (m, 3H), 3.92-3.89 (m, 1H), 3.78-3.76 (m, 1H), 3.71 (s, 3H), 3.22-3.20 (m, 1H), 2.93-2.91 (m, 1H), 2.75-2.73 (m, 2H), 2.58 (s, 2H), 2.52 (s, 3H), 1.97-1.90 (m, 2H), 1.28 (s, 6H), 0.91 (d, J=5.5 Hz, 6H).

Workup

  1. customThe mixture was evaporated under reduced pressure
  2. extractionThe resulting residue was extracted with ethyl acetate (2×10 mL)
  3. concentrationThe combined organic layer was concentrated under reduced pressure
  4. customthe residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-d7294540f4594a8d9902bf93f1784f22
Source dataset
uspto-grants-2015_08
Patent number
US09115152B2

Reaction notes

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