Water → HCID 178523572, compound

HRID 2368796Notes

Reaction equation

HRID 2368796 reaction equation
[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[CH2:4][C:5]1[CH:6]=[C:7]([C:20](=[O:27])[CH:21]=[C:22]([OH:26])[C:23](O)=[O:24])[C:8](=[O:19])[N:9]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[CH:10]=1.[OH:33][C:34]1[C:42]2[N:41]=NN[C:38]=2[CH:37]=[CH:36]C=1.C([O-])(O)=O.[Na+].O>CN(C)C=O.C(Cl)(Cl)Cl>[F:1][C:2]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:3]=1[CH2:4][C:5]1[CH:6]=[C:7]([C:20](=[O:27])[CH:21]=[C:22]([OH:26])[C:23]([NH:41][C@H:42]2[CH2:38][CH2:37][CH2:36][C@@H:34]2[OH:33])=[O:24])[C:8](=[O:19])[N:9]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])[CH:10]=1

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 178418300HCID 178418300, compoundHCID 178525986HCID 178525986, compound

Product 1

HCID 178523572HCID 178523572, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

To a chilled solution of the 4-(1-(2-fluorobenzyl)-5-(4-fluorobenzyl)-2-oxo-1,2-dihydropyridin-3-yl)-2-hydroxy-4-oxobut-2-enoic acid 8 (150 mg, 0.338 mmol) in dimethylformamide (DMF) (2.0 mL), was added hydroxybenzotriazole (HOBT) (50 mg, 0.372 mmol), followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride EDCI-HCl (71 mg, 0.372 mmol). The resulting mixture was stirred for 30 min. A solution of (1S,2S)-(+)-trans-2-aminocyclopentanol hydrochloride and NaHCO3 (31 mg, 0.372 mmol) was added. The resulting mixture was stirred for 2 h at 0-5° C. Thin layer chromatography (TLC) analysis indicated completion, hence cold water was added to the reaction mixture and then extracted with ethyl acetate (2×20 mL). The combined organic phase was separated and washed with water twice, then once with 1N HCl solution, then saturated aqueous NaHCO3 solution. Concentration in vacuo afforded the crude product which was passed through a short plug of silica gel eluting with chloroform, the eluent was concentrated and the residual triturated with hexanes affording the product as a yellow solid in 117 mg (66.0%). The residual solvent was removed in vacuo affording pure product as a yellow solid, mp 60.0-62.9° C., [α]20D +24.0 (c 0.01, MeOH), UV (MeOH) 396 nm (ε 14,455), 318 nm (ε 6327). 1H NMR (CDCl3, 500 MHz): δ 15.33 (bs, 1H), 8.16 (d, 1H, J=2.0 Hz), 8.08 (s, 1H), 7.61-6.85 (m, 9H), 5.22 (s, 2H), 4.11 (m, 1H), 3.94 (m, 1H), 3.78 (s, 1H), 2.23 (m, 1H), 2.10 (m, 1H), 1.88 (m, 1H), 1.78 (m, 2H), 1.59 (m, 1H). 13C NMR (CDCl3, 125 MHz): δ 181.3, 180.6, 163.4, 163.3, 162.4, 162.1, 162.0, 161.4, 161.3, 160.4, 160.1, 160.0, 159.2, 145.5, 143.9, 142.3, 141.6, 132.4, 132.4, 132.3, 131.5, 131.4, 131.3, 131.3, 131.2, 130.7, 130.6, 125.0, 124.9, 124.8, 122.8, 122.7, 122.5, 122.2, 122.2, 122.1, 122.1, 117.1, 115.9, 115.7, 115.6, 111.9, 111.9, 111.8, 111.7, 104.7, 104.5, 104.3, 98.3, 79.5, 79.3, 61.0, 60.6, 51.5, 47.7, 47.3, 32.9, 32.8, 32.7, 30.8, 30.7, 30.5, 21.7, 21.5. HRMS (M+H)+ calculated mass 527.1794 for C28H26F3N2O5. found 527.1799.

Workup

  1. stirringThe resulting mixture was stirred for 2 h at 0-5° C
  2. additionwas added to the reaction mixture
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. customThe combined organic phase was separated
  5. washwashed with water twice
  6. concentrationConcentration in vacuo
  7. customafforded the crude product which
  8. concentrationthe eluent was concentrated
  9. customthe residual triturated with hexanes affording the product as a yellow solid in 117 mg (66.0%)
  10. customThe residual solvent was removed in vacuo
  11. customaffording pure product as a yellow solid, mp 60.0-62.9° C., [α]20D +24.0 (c 0.01, MeOH), UV (MeOH) 396 nm (ε 14,455), 318 nm (ε 6327)

Sources & evidence

ORD record
ord-6316af53918a4a7493979c0c106c4158
Source dataset
uspto-grants-2014_04
Patent number
US08703801B2

Reaction notes

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