Lithium Hydroxide → HCID 86675919, compound

HRID 572664Notes

Reaction equation

HRID 572664 reaction equation
C([O:4][C@@H:5]([CH3:41])[C:6]([NH:8][CH2:9][C@@H:10]1[CH2:15][O:14][C@@H:13]([C@H:16]2[O:20][N:19]=[C:18]([C:21]3[CH:26]=[C:25]([C:27](=[O:39])[NH:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([F:36])=[C:32]([O:37][CH3:38])[CH:31]=4)[N:24]=[C:23]([CH3:40])[N:22]=3)[CH2:17]2)[CH2:12][O:11]1)=[O:7])(=O)C.[OH-].[Li+]>C(#N)C.CCOC(C)=O>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][NH:28][C:27]([C:25]2[CH:26]=[C:21]([C:18]3[CH2:17][C@@H:16]([C@H:13]4[CH2:12][O:11][C@H:10]([CH2:9][NH:8][C:6](=[O:7])[C@@H:5]([OH:4])[CH3:41])[CH2:15][O:14]4)[O:20][N:19]=3)[N:22]=[C:23]([CH3:40])[N:24]=2)=[O:39])=[CH:31][C:32]=1[O:37][CH3:38]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 86675918HCID 86675918, compound

Product 1

HCID 86675919HCID 86675919, compoundYield 53.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (S)-1-(((2R,5R)-5-((S)-3-(6-(4-fluoro-3-methoxybenzylcarbamoyl)-2-methylpyrimidin-4-yl)-4,5-dihydroisoxazol-5-yl)-1,4-dioxan-2-yl)methylamino)-1-oxopropan-2-yl acetate (0.11 g, 0.192 mmol) in ACN (3 mL) was added 2.5M lithium hydroxide (1.151 mL, 2.88 mmol) at RT. The reaction mixture was stirred for 3 h, diluted with EtOAc (25 mL) and washed with brine solution (2×15 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The resulting crude material was purified by preparative TLC eluting with 100% EtOAc to afford N-(4-fluoro-3-methoxybenzyl)-6-((S)-5-((2R,5R)-5-(((S)-2-hydroxypropanamido) methyl)-1,4-dioxan-2-yl)-4,5-dihydroisoxazol-3-yl)-2-methylpyrimidine-4-carboxamide 0.055 g (52%); 1H NMR (400 MHz, DMSO): δ 9.48 (t, J=6.4 Hz, 1H), 8.13 (s, 3H), 7.68 (t, 1H), 7.17-7.13 (m, 2H), 6.88 (m, 1H), 5.5 (d, J=4.8 Hz, 1H), 4.81-4.75 (m, 1H), 4.48 (d, J=6.0 Hz, 2H), 3.96-3.86 (m, 2H), 3.81 (s, 3H), 3.76-3.73 (m, 1H), 3.66-3.63 (m, 1H), 3.52-3.3.36 (m, 4H), 3.29-3.11 (m, 1H), 3.09 (m, 2H), 2.75 (s, 3H), 1.19 (d, J=6.8 Hz, 3H); LC/MS (Table 1, method c) Rt=2.89 min; MS: m/z 532 (m+H)+.

Workup

  1. washwashed with brine solution (2×15 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting crude material was purified by preparative TLC
  5. washeluting with 100% EtOAc

Sources & evidence

ORD record
ord-0a1297ff224a4b7e871244a8d06ae835
Source dataset
uspto-grants-2015_05
Patent number
US09029409B2

Reaction notes

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