HCID 58015339, compound → HCID 54713645, compound

HRID 2171759Notes

Reaction equation

HRID 2171759 reaction equation
[Na].[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[CH2:10][NH:11][C:12]([C:14]1[C:15](=[O:30])[C:16]([OH:29])=[C:17]2[C:22](=[O:23])[N:21]3[C@H:24]([CH3:27])[CH2:25][O:26][C@H:20]3[CH2:19][N:18]2[CH:28]=1)=[O:13].FC1C=C(F)C=CC=1CNC(C1C(=O)C(OCC2C=CC=CC=2)=C2C(=O)N3[C@H](C)CO[C@H]3CN2C=1)=O>CO.[Pd]>[F:2][C:3]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:4]=1[CH2:10][NH:11][C:12]([C:14]1[C:15](=[O:30])[C:16]([OH:29])=[C:17]2[C:22](=[O:23])[N:21]3[C@H:24]([CH3:27])[CH2:25][O:26][C@H:20]3[CH2:19][N:18]2[CH:28]=1)=[O:13]

Participants

5

Reactant 2

HCID 58015339HCID 58015339, compoundHCID 66594195HCID 66594195, compound

Product 1

HCID 54713645HCID 54713645, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

(3R,11aS)—N-[(2,4-Difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide sodium salt. To a solution of (3R,11aS)—N-[(2,4-difluorophenyl)methyl]-3-methyl-5,7-dioxo-6-[(phenylmethyl)oxy]-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide (396 mg, 0.80 mmol) in methanol (30 mL) was added 10% Pd/C (25 mg). Hydrogen was bubbled through the reaction mixture via a balloon for 2 h. The resultant mixture was filtered through Celite with methanol and dichloromethane. The filtrate was concentrated in vacuo to give (3R,11aS)—N-[(2,4-difluorophenyl)methyl]-6-hydroxy-3-methyl-5,7-dioxo-2,3,5,7,11,11a-hexahydro[1,3]oxazolo[3,2-a]pyrido[1,2-d]pyrazine-8-carboxamide as a pink tinted white solid (278 mg, 86%). 1H NMR (CDCl3) δ 11.47 (m, 1H), 10.29 (m, 1H), 8.32 (s, 1H), 7.36 (m, 1H), 6.82 (m, 2H), 5.31 (dd, J=9.6, 3.6 Hz, 1H), 4.65 (m, 2H), 4.47-4.38 (m, 3H), 3.93 (dd, J=12.0, 10.0 Hz, 1H), 3.75 (m, 1H), 1.49 (d, J=5.6 Hz, 3H); ES+ MS: 406 (M+1). The above material (278 mg, 0.66 mmol) was taken up in ethanol (10 mL) and treated with 1 N sodium hydroxide (aq) (0.66 mL, 0.66 mmol). The resulting suspension was stirred at room temperature for 30 min. Ether was added and the liquids were collected to provide the sodium salt of the title compound as a white powder (291 mg, 99%). 1H NMR (DMSO-d6) δ 10.68 (m, 1H), 7.90 (s, 1H), 7.35 (m, 1H), 7.20 (m, 1H), 7.01 (m, 1H), 5.20 (m, 1H), 4.58 (m, 1H), 4.49 (m, 2H), 4.22 (m, 2H), 3.74 (dd, J=11.2, 10.4 Hz, 1H), 3.58 (m, 1H), 1.25 (d, J=4.4 Hz, 3H).

Workup

  1. customHydrogen was bubbled through the reaction mixture via a balloon for 2 h
  2. filtrationThe resultant mixture was filtered through Celite with methanol and dichloromethane
  3. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-7e404d5180d14d6d98b581737a1d8088
Source dataset
uspto-grants-2015_06
Patent number
US09051337B2

Reaction notes

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