Water → HCID 58043750, compound

HRID 1919106Notes

Reaction equation

HRID 1919106 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH:31]5[CH2:34][O:33][CH2:32]5)[CH2:27][CH2:26]4)=[CH:21][N:20]=3)[C:15](=[O:35])[N:14]([CH3:36])[CH:13]=2)=[CH:10][C:9]([F:37])=[CH:8][C:7]=1[N:38]1[CH2:49][CH2:48][N:47]2[C:40](=[CH:41][C:42]3[CH2:43][C:44]([CH3:51])([CH3:50])[CH2:45][C:46]=32)[C:39]1=[O:52])(=O)C.O.[Li+].[OH-]>C1COCC1>[F:37][C:9]1[CH:10]=[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([N:25]4[CH2:30][CH2:29][N:28]([CH:31]5[CH2:32][O:33][CH2:34]5)[CH2:27][CH2:26]4)=[CH:21][N:20]=3)[C:15](=[O:35])[N:14]([CH3:36])[CH:13]=2)[C:6]([CH2:5][OH:4])=[C:7]([N:38]2[CH2:49][CH2:48][N:47]3[C:40](=[CH:41][C:42]4[CH2:43][C:44]([CH3:50])([CH3:51])[CH2:45][C:46]=43)[C:39]2=[O:52])[CH:8]=1

Participants

5

Reactant 3

HCID 962Water2×HCID 3939Lithium HydroxideHCID 86762202HCID 86762202, compound

Product 1

HCID 58043750HCID 58043750, compoundYield 53.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-4-fluoro-6-[1-methyl-5-({5-[4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl}amino)-6-oxo-1,6-dihydropyridin-3-yl]phenyl)methyl acetate (200 mg, 0.28 mmol) in THF/iPA/H2O (6 mL/6 mL/2 mL) at room temperature was added LiOH (70 mg, 2.9 mmol) while stirring. This mixture was stirred for 0.5 h. Then, 20 mL H2O was added and the mixture was extracted with ethyl acetate (30 mL×3). The combined organic layers were dried with Na2SO4 and concentrated to give a yellow solid which was further purified by prep-HPLC to afford 304 as a white solid (100 mg, 53%). LCMS: [M+H]+ 668. 1H NMR (500 MHz, DMSO): δ 1.23 (s, 6H), 2.37-2.39 (m, 5H), 2.53-2.57 (m, 2H), 3.07 (s, 4H), 3.43-3.45 (m, 2H), 3.60 (s, 3H), 3.85-3.87 (m, 1H), 4.16-1.19 (m, 3H), 4.32 (d, J=6.0 Hz, 2H), 4.45-4.50 (m, 2H), 4.54-4.58 (m, 2H), 4.86 (s, 1H), 6.47-6.51 (m, 1H), 7.18-7.25 (m, 2H), 7.34-7.39 (m, 3H), 7.83-7.86 (m, 1H), 8.35-8.37 (m, 1H), 8.53-8.56 (m, 1H).

Workup

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

Sources & evidence

ORD record
ord-d6b2ea9359264167a0947b7a15e26641
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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