Triethylamine → HCID 67298215, compound

HRID 1520341Notes

Reaction equation

HRID 1520341 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Cl:12])[CH:10]=2)[N:5]=[C:4]([C:13]2[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=2)[N:3]=1.[NH2:19][C:20]1[CH:32]=[CH:31][CH:30]=[CH:29][C:21]=1[C:22]([NH:24][CH2:25][CH:26]1[CH2:28][CH2:27]1)=[O:23].CCN(CC)CC>CC(O)C>[Cl:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[C:4]([C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)[N:3]=[C:2]2[NH:19][C:20]1[CH:32]=[CH:31][CH:30]=[CH:29][C:21]=1[C:22]([NH:24][CH2:25][CH:26]1[CH2:28][CH2:27]1)=[O:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10401205HCID 10401205, compoundHCID 16795478HCID 16795478, compound

Product 1

HCID 67298215HCID 67298215, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A 100 mL round bottom flask was charged with 4,6-dichloro-2-(pyridin-3-yl)quinazoline (synthesized as described in Scheme 1 and 4, substituting 5-chloro-2-nitrobenzoic acid for 2-nitro-5-propoxy-benzoic acid) (150 mg, 0.54 mmol) and 2-amino-N-(cyclopropylmethyl)benzamide) (310 mg, 1.63 mmol) and anhydrous i-PrOH (20 mL) was added and refluxed for 3 h. The reaction mixture was cooled to room temperature and Et3N (3 eq) was added. The solvent was removed in vacuo. To the crude product was added a water-methanol mixture (5:1, 50 mL), and then sonicated for 5 min. The solidified compound was collected by filtration, and the solid was recrystallized from hot methanol and washed with water. The product was dried at 50° C. to give 2-(6-chloro-2-(pyridin-3-yl)quinazolin-4-ylamino)-N-(cyclopropylmethyl)benzamide as a colorless cotton (220 mg, 94%). The structure was confirmed by NMR and elemental analysis. 1H NMR (Bruker 300 MHz, DMSO-d6) ppm 0.20-0.98 (m, 5H), 3.07-3.21 (m, 2H), 7.24-8.26 (m, 7H), 8.68-9.55 (m, 5H), 12.22 (s, 1H). CHN Calcd. C, 67.05; H, 4.69; N, 16.29. Found C, 67.15; H, 4.89; N, 16.25

Workup

  1. additionwas added
  2. temperaturerefluxed for 3 h
  3. customThe solvent was removed in vacuo
  4. additionTo the crude product was added a water-methanol mixture (5:1, 50 mL)
  5. customsonicated for 5 min
  6. filtrationThe solidified compound was collected by filtration
  7. customthe solid was recrystallized from hot methanol
  8. washwashed with water
  9. customThe product was dried at 50° C.

Sources & evidence

ORD record
ord-b72f4639ccad473dbe3c7db48885c707
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

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