3-Chlorobenzaldehyde → 2-(6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-(3-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetic acid

HRID 77378Notes

Reaction equation

[NH2:1][C:2]1[CH:14]=[CH:13][C:12]([N:15]2[CH:21]3[CH2:22][CH2:23][N:18]([CH2:19][CH2:20]3)[CH2:17][CH2:16]2)=[CH:11][C:3]=1[C:4]([NH:6][CH2:7][C:8]([OH:10])=[O:9])=[O:5].[Cl:24][C:25]1[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=1)[CH:28]=O>C(O)C.C(O)(=O)C.CO.[O-2].[O-2].[Mn+4]>[N:18]12[CH2:23][CH2:22][CH:21]([CH2:20][CH2:19]1)[N:15]([C:12]1[CH:11]=[C:3]3[C:2](=[CH:14][CH:13]=1)[N:1]=[C:28]([C:27]1[CH:30]=[CH:31][CH:32]=[C:25]([Cl:24])[CH:26]=1)[N:6]([CH2:7][C:8]([OH:10])=[O:9])[C:4]3=[O:5])[CH2:16][CH2:17]2

Participants

Conditions

Temperature: 85 °C

Procedure

2-(2-Amino-5-(1,4-diazabicyclo[3.2.2]nonan-4-yl)benzamido)acetic acid (85.3 mg, 0.27 mmol) (Intermediate 9A) was dissolved in ethanol (3 mL). 3-Chlorobenzaldehyde (56.5 mg, 0.046 mL, 0.40 mmol) was added followed by 2 drops of acetic acid. The reaction mixture was refluxed at 85° C. overnight. The reaction mixture was diluted with methanol and purified directly using a 1 g SCX cartridge. The crude material was concentrated to dryness before re-dissolving in dichloromethane and manganese dioxide (18.8 mg, 0.32 mmol) added. The solution was then stirred overnight before filtering and concentrated under reduced pressure to give 2-(6-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-(3-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetic acid (54 mg, 0.12 mmol).

Workup

custompurified directly
concentrationThe crude material was concentrated to dryness
dissolutionbefore re-dissolving in dichloromethane
filtrationbefore filtering
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-4dba041d2ca8492498f8f8b97bba1c87
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841289B2

Reaction notes

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