Cesium carbonate → N-(2-(1-hydroxycyclopentyl)-1,7-naphthyridin-6-yl)cyclopropanecarboxamide

HRID 1502409Notes

Reaction equation

HRID 1502409 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[C:7]([C:12]1([OH:17])[CH2:16][CH2:15][CH2:14][CH2:13]1)[CH:6]=[CH:5]2.[CH:18]1([C:21]([NH2:23])=[O:22])[CH2:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C>[OH:17][C:12]1([C:7]2[CH:6]=[CH:5][C:4]3[C:9](=[CH:10][N:11]=[C:2]([NH:23][C:21]([CH:18]4[CH2:20][CH2:19]4)=[O:22])[CH:3]=3)[N:8]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 866749671-(6-Chloro-1,7-naphthyridin-2-yl)cyclopentanol

Product 1

HCID 57523996N-(2-(1-hydroxycyclopentyl)-1,7-naphthyridin-6-yl)cyclopropanecarboxamideYield 45.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1-(6-chloro-1,7-naphthyridin-2-yl)cyclopentanol (65 mg, 0.26 mmol), cyclopropanecarboxamide (67 mg, 0.8 mmol), Chloro[2-(dicyclohexylphosphino)-3-,6-dimethoxy-2,4′-6′-tri-1-pr-1,1′-biphenyl)][2-(2-aminoethyl )Ph]Pd(II) (31 mg, 0.04 mmol), (dicyclohexylphosphino)-3-,6-dimethoxy-2,4′-6′-tri-i-pr-1,1′-biphenyl (21 mg, 0.04 mmol), and cesium carbonate (170 mg, 0.52 mmol) in 1,4-dioxane (1.5 mL) was heated at 90° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as an off-white solid (35 mg, 45%). 1H NMR (400 MHz, DMSO) δ 10.97 (s, 1H), 9.12 (s, 1H), 8.47 (s, 1H), 8.30 (d, J=8.8 Hz, 1H), 8.00 (d, J=8.8 Hz, 1H), 5.32 (s, 1H), 2.29-2.17 (m, 2H), 2.11-2.03 (m, 1H), 1.95-1.75 (m, 6H), 0.91-0.78 (m, 4H). LCMS (Method E): RT=3.811 min, M+H+=298.1.

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water (50 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

Sources & evidence

ORD record
ord-4d630b76231840dea0db9695bca94a91
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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