Water → Methyl 2-(7-(2-((tert-butoxycarbonyl)amino)acetyl)-4-chloro-5,6,7,8-tetrahydro-1,7-naphthyridin-8-yl)acetate

HRID 532922Notes

Reaction equation

HRID 532922 reaction equation
[Cl:1][C:2]1[C:11]2[CH2:10][CH2:9][NH:8][CH:7]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[C:6]=2[N:5]=[CH:4][CH:3]=1.[C:17]([NH:24][CH2:25][C:26](O)=[O:27])([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(N(CC)CC)C.O>CCOC(C)=O.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CN(C=O)C>[C:20]([O:19][C:17]([NH:24][CH2:25][C:26]([N:8]1[CH:7]([CH2:12][C:13]([O:15][CH3:16])=[O:14])[C:6]2[N:5]=[CH:4][CH:3]=[C:2]([Cl:1])[C:11]=2[CH2:10][CH2:9]1)=[O:27])=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 78288N-(tert-butoxycarbonyl)glycineHCID 86711366HCID 86711366, compound

Product 1

HCID 86711368Methyl 2-(7-(2-((tert-butoxycarbonyl)amino)acetyl)-4-chloro-5,6,7,8-tetrahydro-1,7-naphthyridin-8-yl)acetateYield 96.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 111923Propylphosphonic anhydrideSolvent

Procedure

94-6. To a stirred solution of methyl 2-(4-chloro-5,6,7,8-tetrahydro-1,7-naphthyridin-8-yl)acetate (320 mg, 1.33 mmol), Boc-glycine (233 mg, 1.33 mmol) and triethylamine (0.37 mL, 2.66 mmol) in AcOEt (7 mL), T3P (0.93 mL, 1.59 mmol, 50% m/m in DMF) was added and the solution was stirred at RT for 16 h. Water was added and the mixture was extracted with AcOEt (2×). The combined organic layers were dried with sodium sulfate, filtered and the solvent was removed under reduced pressure. The crude product was purified by flash-column chromatography over silicagel (Biotage Isolera One, eluent: gradient from 0% AcOEt in cyclohexane to 100% AcOEt in cyclohexane in 21 min) to yield the title compound as a clear oil (510 mg). UPLC-MS: MS 398.1 (M+H+); UPLC rt 0.95 min.

Workup

  1. extractionthe mixture was extracted with AcOEt (2×)
  2. dry with materialThe combined organic layers were dried with sodium sulfate
  3. filtrationfiltered
  4. customthe solvent was removed under reduced pressure
  5. customThe crude product was purified by flash-column chromatography over silicagel (Biotage Isolera One, eluent: gradient from 0% AcOEt in cyclohexane to 100% AcOEt in cyclohexane in 21 min)

Sources & evidence

ORD record
ord-0343e7fc447a43c2a101b35926d29ab3
Source dataset
uspto-grants-2014_10
Patent number
US08853203B2

Reaction notes

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