Sodium Bicarbonate → (R)-N-(4-Fluoro-2-(2-(hydroxymethyl)-5-oxopyrrolidin-1-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide

HRID 348216Notes

Reaction equation

HRID 348216 reaction equation
[Si]([O:8][CH2:9][C@H:10]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]1[C:16]1[CH:46]=[C:45]([F:47])[CH:44]=[CH:43][C:17]=1[CH2:18][NH:19][C:20]([C:22]1[N:23]=[C:24]2[N:29]([C:30](=[O:40])[C:31]=1[O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[CH2:28][CH2:27][O:26][C:25]2([CH3:42])[CH3:41])=[O:21])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(O)=O.[Na+]>O1CCCC1>[F:47][C:45]1[CH:44]=[CH:43][C:17]([CH2:18][NH:19][C:20]([C:22]2[N:23]=[C:24]3[N:29]([C:30](=[O:40])[C:31]=2[O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:28][CH2:27][O:26][C:25]3([CH3:42])[CH3:41])=[O:21])=[C:16]([N:11]2[C:12](=[O:15])[CH2:13][CH2:14][C@@H:10]2[CH2:9][OH:8])[CH:46]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 58777352HCID 58777352, compound

Product 1

HCID 58777341(R)-N-(4-Fluoro-2-(2-(hydroxymethyl)-5-oxopyrrolidin-1-yl)benzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamideYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

To a stirred solution of intermediate 166, (R)-N-(2-(2-((tert-butyldimethylsilyloxy)methyl)-5-oxopyrrolidin-1-yl)-4-fluorobenzyl)-3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.10 g, 0.150 mmol) in tetrahydrofuran (5 mL) at 23° C. was added a solution of tetrabutylammonium fluoride (1M in tetrahydrofuran) (180 μL, 0.18 mmol). The reaction mixture was stirred at 23° C. for 3 h. NaHCO3 (1N in H2O, 30 mL) was then added and the organic material was extracted with ethyl acetate (2×25 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. The residue was purified on a Biotage system using a silica gel column with ethyl acetate/Hexanes (1:1) to ethyl acetate 100% as eluent to afford the title compound (0.060 g, 73% yield): 1HNMR 400 MHz (MeOD) δ (ppm): 7.55 (1H, dd, (t), 6.6 Hz), 7.43 (2H, m), 7.13 (1H, dd, J=9.5, 2.4 Hz), 7.03 (1H, m), 5.26 (2H, s), 4.57 (1H, m), 4.32 (2H, m), 4.08 (2H, t, J=5.0 Hz), 7.03 (2H, t, J=5.0 Hz), 3.53 (2H, m), 2.69–2.56 (2H, m), 2.38 (1H, m), 2.22 (1H, m), 1.62 (6H, s). LCMS (M+H)+ m/z 551.

Workup

  1. extractionthe organic material was extracted with ethyl acetate (2×25 mL)
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified on a Biotage system

Sources & evidence

ORD record
ord-c9adba61689d43e49be34afe94b24a9b
Source dataset
uspto-grants-2007_02
Patent number
US07176196B2

Reaction notes

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