1-Hydroxybenzotriazole → 6-cyano-4-oxo-N-[[3-[[[2-(1H-1,2,4-triazol-5-yl)acetyl]amino]methyl]phenyl]methyl]-1H-quinazoline-2-carboxamide

HRID 606392Notes

Reaction equation

HRID 606392 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH2:10][NH:11][C:12]([C:14]2[NH:23][C:22](=[O:24])[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([C:25]#[N:26])[CH:20]=3)[N:15]=2)=[O:13])[CH:7]=[CH:8][CH:9]=1.[NH:27]1[CH:31]=[N:30][C:29]([CH2:32][C:33](O)=[O:34])=[N:28]1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>CN(C=O)C>[C:25]([C:19]1[CH:20]=[C:21]2[C:16](=[CH:17][CH:18]=1)[N:15]=[C:14]([C:12]([NH:11][CH2:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([CH2:3][NH:2][C:33](=[O:34])[CH2:32][C:29]3[N:30]=[CH:31][NH:27][N:28]=3)[CH:5]=1)=[O:13])[NH:23][C:22]2=[O:24])#[N:26]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 136380963N-{[3-(aminomethyl)phenyl]methyl}-6-cyano-4-oxo-3,4-dihydroquinazoline-2-carboxamide hydrochlorideHCID 1785252442-(1H-1,2,4-triazol-3-yl)acetic acid

Product 1

HCID 1785094956-cyano-4-oxo-N-[[3-[[[2-(1H-1,2,4-triazol-5-yl)acetyl]amino]methyl]phenyl]methyl]-1H-quinazoline-2-carboxamideYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

A solution of N-{[3-(aminomethyl)phenyl]methyl}-6-cyano-4-oxo-3,4-dihydroquinazoline-2-carboxamide hydrochloride obtained in Reference Example 47 (170 mg, 0.460 mmol), 1H-1,2,4-triazol-3-ylacetic acid obtained in Reference Example 15 (70.0 mg, 0.551 mmol), diisopropylethylamine (0.079 mL, 0.460 mmol), 1-[3-(dimethylamino)propyl]-3-ethyl-carbodiimide hydrochloride (106 mg, 0.550 mmol) and 1-hydroxybenzotriazole (74.0 mg, 0.550 mmol) in DMF (10 mL) was stirred at 40° C. for 15 hr. The reaction mixture was concentrated under reduced pressure, and water was added to the residue. The resulting solid was collected by filtration, washed with water and IPE, and dried. The obtained crude crystals were recrystallized from ethyl acetate-IPE to give the title compound as a white powder (49.4 mg, 24%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and water
  2. additionwas added to the residue
  3. filtrationThe resulting solid was collected by filtration
  4. washwashed with water and IPE
  5. customdried
  6. customThe obtained crude crystals
  7. customwere recrystallized from ethyl acetate-IPE

Sources & evidence

ORD record
ord-820bbeeb5ece489db2ba65d41f3015d6
Source dataset
uspto-grants-2011_03
Patent number
US07915267B2

Reaction notes

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