Triphenylphosphine → 2-(3-chlorophenyl)-3-methyl-6-(quinuclidin-3-yloxy)quinazolin-4(3H)-one

HRID 77410

Reaction equation

HRID 77410 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]([CH3:18])[C:16](=[O:19])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([OH:20])[CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[N:21]12[CH2:28][CH2:27][CH:24]([CH2:25][CH2:26]1)[CH:23](O)[CH2:22]2.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>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:17]([CH3:18])[C:16](=[O:19])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:20][CH:23]4[CH:24]5[CH2:27][CH2:28][N:21]([CH2:26][CH2:25]5)[CH2:22]4)[CH:14]=3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 15381(+-)-3-QuinuclidinolHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 699287212-(3-chlorophenyl)-6-hydroxy-3-methylquinazolin-4(3H)-one2×

Product 1

HCID 513533152-(3-chlorophenyl)-3-methyl-6-(quinuclidin-3-yloxy)quinazolin-4(3H)-oneYield 12.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(3-chlorophenyl)-6-hydroxy-3-methylquinazolin-4(3H)-one (Intermediate 33A) (100 mg, 0.35 mmol), 3-quinuclidinol (44 mg, 0.35 mmol) and triphenylphosphine (137 mg, 0.35 mmol) in tetrahydrofuran (2 mL) was added dropwise diisopropyl azodicarboxylate (0.103 mL, 0.52 mmol). The reaction was stirred for 20 h. The mixture was purified by scx cartridge (1 g) followed by acidic prep hplc then scx (500 mg) to afford 2-(3-chlorophenyl)-3-methyl-6-(quinuclidin-3-yloxy)quinazolin-4(3H)-one (18 mg, 0.045 mmol).

Workup

  1. customThe mixture was purified by scx cartridge (1 g)

Sources & evidence

ORD record
ord-8bfe56b1768448508a09fe381435f52e
Source dataset
uspto-grants-2014_09
Patent number
US08841289B2

Linked notes

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