Triethylamine → HCID 21103208, compound

HRID 1354804Notes

Reaction equation

HRID 1354804 reaction equation
[C:1]1([C:7]2[C:8]([C:17]3[CH:25]=[CH:24][C:20]([C:21](O)=[O:22])=[CH:19][CH:18]=3)=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][N:11]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN(CC)CC.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.O.CO>[C:1]1([C:7]2[C:8]([C:17]3[CH:18]=[CH:19][C:20]([CH2:21][OH:22])=[CH:24][CH:25]=3)=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[CH:12][N:11]=3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 21103207HCID 21103207, compound

Product 1

HCID 21103208HCID 21103208, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-(3-phenyl-1,8-naphthyridin-2-yl)benzoic acid (9-1) (100 mg, 0.31 mmole) in dry THF (1.5 mL) was added Et3N (0.056 mL, 0.4 mmole) then isobutyl chloroformate (0.048 mL, 0.37 mmole) at 0° C. After 30 min the mixture was warmed to RT. After 30 min NaBH4 (35 mg, 0.92 mmole) was added then MeOH (1 mL) very slowly (vigorous gas evolution). After 1 hr the mixture was diluted with H2O. The pH was adjusted to 7 and the mixture extracted with CH2Cl2 (5×). The combined organic layers were dried (MgSO4), filtered, and concentrated. The reaction was repeated using 320 mg 4-(3-phenyl-1,8-naphthyridin-2-yl)benzoic acid (9-1). After work-up the crude products were combined then purified by flash column chromatography (gradient, 0–5% MeOH/CH2Cl2) to give the title compound as a yellow foam (9-2): 1H-NMR (500 MHz, CDCl3) δ 9.14 (m, 1 H), 8.24 (m, 1 H), 8.19 (s, 1 H), 7.55 (d, J=7.81 Hz, 2 H), 7.51 (m, 1 H), 7.33 (m, 3 H), 7.27 (m, 4 H), 4.70 (s, 2 H).

Workup

  1. customat 0° C
  2. extractionthe mixture extracted with CH2Cl2 (5×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customAfter work-up the crude products were combined then purified by flash column chromatography (gradient, 0–5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-ea24d999d0a444789f4e1f41675b399d
Source dataset
uspto-grants-2007_05
Patent number
US07223738B2

Reaction notes

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