Triphenylphosphine → Methyl 5-4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxynicotinate

HRID 2102379Notes

Reaction equation

HRID 2102379 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[CH3:15][O:16][C:17](=[O:25])[C:18]1[CH:23]=[C:22]([OH:24])[CH:21]=[N:20][CH:19]=1.[F:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[C:41]3[C:40]([CH2:42][CH2:43][CH2:44][CH2:45]O)=[N:39][CH:38]=[N:37][C:36]=3[S:35][CH:34]=2)=[CH:29][CH:28]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[F:26][C:27]1[CH:28]=[CH:29][C:30]([C:33]2[C:41]3[C:40]([CH2:42][CH2:43][CH2:44][CH2:45][O:24][C:22]4[CH:21]=[N:20][CH:19]=[C:18]([CH:23]=4)[C:17]([O:16][CH3:15])=[O:25])=[N:39][CH:38]=[N:37][C:36]=3[S:35][CH:34]=2)=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 354317Methyl 5-hydroxypyridine-3-carboxylateHCID 115512134-[5-(4-Fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butan-1-ol

Product 1

HCID 11647803Methyl 5-4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxynicotinateYield 8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropyl azodicarboxylate (0.040 g, 0.20 mmol) was added to a mixture of 5-hydroxynicotinic acid methyl ester (0.038 g, 0.25 mmol), 4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butan-1-ol (0.060 g, 0.20 mmol), triphenylphosphine (0.052 g, 0.20 mol) and tetrahydrofuran (3.0 mL) at room temperature with stirring. After 16 h, the solvent was removed in vacuo. The residue was diluted with ethyl acetate (50 mL) and washed with sodium bicarbonate (1×40 mL). The organic solution was concentrated and purified by column chromatography (1.5-5% methanol/dichloromethane) to give 7 mg (8%) methyl 5-4-[5-(4-fluorophenyl)thieno[2,3-d]pyrimidin-4-yl]butoxynicotinate as white solid. MS [M+H]=438.1, LC/MS (EI) tR 4.63 min (Method D), 1H NMR (CDCl3) δ (ppm) 9.02 (s, 1H), 8.82 (s, 1H), 8.38 (s, 1H), 7.68 (s, 1H), 7.42-7.35 (m, 2H), 7.34 (s, 1H), 7.20-7.10 (m, 2H), 3.97 (s, 3H), 3.88 (t, J=6.3 Hz, 2H), 2.72 (t, J=7.2 Hz, 2H), 1.81-1.66 (m, 2H), 1.66-1.53 (m, 2H).

Workup

  1. customthe solvent was removed in vacuo
  2. additionThe residue was diluted with ethyl acetate (50 mL)
  3. washwashed with sodium bicarbonate (1×40 mL)
  4. concentrationThe organic solution was concentrated
  5. custompurified by column chromatography (1.5-5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-7856932905e74c7faf63334d00ee1bd3
Source dataset
uspto-grants-2009_08
Patent number
US07576080B2

Reaction notes

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