Lithium Hydroxide → HCID 71558244, compound

HRID 1022005Notes

Reaction equation

HRID 1022005 reaction equation
C([O:4][CH2:5][C:6]1[C:7]([N:38]2[C:50](=[O:51])[C:49]3[S:48][C:47]4[CH2:46][CH2:45][CH2:44][CH2:43][C:42]=4[C:41]=3[CH:40]=[N:39]2)=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[N:23][C:22]([N:25]3[CH2:30][CH2:29][N:28]([CH:31]4[CH2:34][O:33][CH2:32]4)[CH2:27][C@@H:26]3[CH3:35])=[CH:21][N:20]=2)[C:15](=[O:36])[N:14]([CH3:37])[CH:13]=1)(=O)C.[OH-].[Li+]>C(O)(C)C.C1COCC1.O>[OH:4][CH2:5][C:6]1[C:7]([N:38]2[C:50](=[O:51])[C:49]3[S:48][C:47]4[CH2:46][CH2:45][CH2:44][CH2:43][C:42]=4[C:41]=3[CH:40]=[N:39]2)=[N:8][CH:9]=[CH:10][C:11]=1[C:12]1[CH:17]=[C:16]([NH:18][C:19]2[CH:24]=[N:23][C:22]([N:25]3[CH2:30][CH2:29][N:28]([CH:31]4[CH2:32][O:33][CH2:34]4)[CH2:27][C@@H:26]3[CH3:35])=[CH:21][N:20]=2)[C:15](=[O:36])[N:14]([CH3:37])[CH:13]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86684431HCID 86684431, compound

Product 1

HCID 71558244HCID 71558244, compoundYield 46.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 22597222Tetrahydrofuran 2-propanolSolvent

Conditions

Temperature
35 °C

Procedure

A mixture of 230j (80 mg, 0.11 mmol) and lithium hydroxide (27 mg, 1.1 mmol) in i-propanol/THF (1:1, 10 mL) and water (2 mL) was stirred at 35° C. for 0.5 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by reverse-phase prep-HPLC to afford 230 (34 mg, 45%). MS-ESI: [M+H]+ 668.2. 1H NMR (500 MHz, DMSO-d6) δ 8.64 (s, 1H), 8.56 (d, J=6.0 Hz, 1H), 8.46 (s, 1H), 8.40 (d, J=2.5 Hz, 1H), 8.34 (d, J=1.5 Hz, 1H), 7.85 (s, 1H), 7.53 (d, J=6.0 Hz, 1H), 7.49 (d, J=2.5 Hz, 1H), 4.84 (bs, 1H), 4.58-4.54 (m, 2H), 4.50-4.47 (m, 1H), 4.43-4.36 (m, overlap, 4H), 3.78-3.75 (m, 1H), 3.59 (s, 3H), 3.39-3.35 (m, 1H), 3.02-3.0 (m, 1H), 2.98-2.95 (m, 2H), 2.90-2.82 (m, 2H), 2.78-2.76 (m, 1H), 2.60-2.56 (m, 1H), 2.10-2.09 (m, 1H), 1.95-1.88 (m, overlap, 5H), 1.10 (d, J=8.0 Hz, 3H).

Workup

  1. temperatureIt was then cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe resulting residue was purified by reverse-phase prep-HPLC

Sources & evidence

ORD record
ord-7fbfc632c69246e5bc2ddee4e8f21c4f
Source dataset
uspto-grants-2014_05
Patent number
US08716274B2

Reaction notes

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