Triphenylphosphine → 4-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline

HRID 2102812Notes

Reaction equation

HRID 2102812 reaction equation
N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([OH:30])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.[CH3:31][N:32]1[CH2:37][CH2:36][N:35]([CH2:38][CH2:39][CH2:40]O)[CH2:34][CH2:33]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:40][CH2:39][CH2:38][N:35]3[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 792083-(4-Methyl-1-piperazine)propan-1-ol2×HCID 97268Di-tert-butyl azodicarboxylateHCID 1357422514-Chloro-6-methoxyquinazolin-7-ol

Product 1

HCID 112450614-Chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazolineYield 74.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Di-tert-butyl azodicarboxylate (0.478 g, 2.08 mmol) was added portionwise to a mixture of 4-chloro-7-hydroxy-6-methoxyquinazoline (0.350 g, 1.66 mmol), 3-(4-methyl-piperazin-1-yl)-propan-1-ol (Intermediate 9, 0.276 g, 1.74 mmol), and triphenylphosphine (0.544 g, 2.08 mmol) in dichloromethane (20 mL) at r.t. If necessary, further alcohol was added. After stirring for 2 h, the solution was concentrated to 10 mL, mounted on silica and chromatographed (gradient, dichloromethane to dichloromethane:methol=3.2 within 1 h) to obtain 4-chloro-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinazoline (brownish solid, 0.431 g, 1.23 mmol, 74%). LC/ESI-MS: m/z=351 [M(35Cl)+H]+; Rt=1.88 min Cf. also WO 04/143472, page 32,

Workup

  1. concentrationthe solution was concentrated to 10 mL
  2. customchromatographed (gradient, dichloromethane to dichloromethane:methol=3.2 within 1 h)

Sources & evidence

ORD record
ord-24fcbd48f3de4256afa72e24f79ba4f8
Source dataset
uspto-grants-2009_08
Patent number
US07576090B2

Reaction notes

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