Triphenylphosphine → HCID 71115229, compound

HRID 468876Notes

Reaction equation

HRID 468876 reaction equation
O[CH2:2][CH:3]([C:7]1[N:16]=[C:15]([C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[CH3:24])[CH:14]=[C:13]2[C:8]=1[CH:9]=[C:10]([NH:25][C:26]([CH:28]1[CH2:30][CH2:29]1)=[O:27])[N:11]=[CH:12]2)[CH2:4][CH2:5][OH:6].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.C(OCC)(=O)C>[F:23][C:21]1[CH:20]=[CH:19][C:18]([CH3:24])=[C:17]([C:15]2[CH:14]=[C:13]3[C:8]([CH:9]=[C:10]([NH:25][C:26]([CH:28]4[CH2:30][CH2:29]4)=[O:27])[N:11]=[CH:12]3)=[C:7]([CH:3]3[CH2:4][CH2:5][O:6][CH2:2]3)[N:16]=2)[CH:22]=1

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 71115014HCID 71115014, compound

Product 1

HCID 71115229HCID 71115229, compoundYield 25.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(5-(1,4-dihydroxybutan-2-yl)-7-(5-fluoro-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide (45 mg, 0.1 mmol) in tetrahydrofuran (1 mL) was added triphenylphosphine (61 mg, 0.23 mmol) followed by diisopropyl azodicarboxylate (0.028 mL, 0.14 mmol), and the reaction mixture was stirred at room temperature for 1 hour. The 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 flash chromatography (silica, 4 g, ISCO, 0-60% ethyl acetate in heptane) and then repurified 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 (10 mg, 20% over two steps). 1H NMR (400 MHz, DMSO) δ 11.18 (s, 1H), 9.30 (s, 1H), 8.83 (s, 1H), 8.03 (s, 1H), 7.41-7.31 (m, 2H), 7.19 (td, J=8.5, 2.8 Hz, 1H), 4.31-4.23 (m, 1H), 4.20 (t, J=7.7 Hz, 1H), 4.00-3.95 (m, 1H), 3.94-3.86 (m, 2H), 2.42-2.35 (m, 5H), 2.10 (m, 1H), 0.95-0.82 (m, 4H). LCMS (Method E): RT=5.416 min, M+H+=392.2.

Workup

  1. washwashed with water (50 mL)
  2. customThe organic layer was separated
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto afford a residue that
  7. customwas purified by flash chromatography (silica, 4 g, ISCO, 0-60% ethyl acetate in heptane)
  8. customrepurified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

Sources & evidence

ORD record
ord-911d43c3a6ca48f59e039afbe0d13cfb
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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