1-Hydroxybenzotriazole → 4-Anilino-5-chloro-2-{4-{N-[3-(imidazol-1-yl)propyl]carbamoyl}anilino}pyrimidine

HRID 480009Notes

Reaction equation

HRID 480009 reaction equation
[NH:1]([C:8]1[C:13]([Cl:14])=[CH:12][N:11]=[C:10]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([OH:24])=O)=[CH:18][CH:17]=2)[N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:25][CH2:26][CH2:27][CH2:28][N:29]1[CH:33]=[CH:32][N:31]=[CH:30]1.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[NH:1]([C:8]1[C:13]([Cl:14])=[CH:12][N:11]=[C:10]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:22](=[O:24])[NH:25][CH2:26][CH2:27][CH2:28][N:29]3[CH:33]=[CH:32][N:31]=[CH:30]3)=[CH:18][CH:17]=2)[N:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 787361H-Imidazole-1-propanamineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18768041HCID 18768041, compound

Product 1

HCID 187680634-Anilino-5-chloro-2-{4-{N-[3-(imidazol-1-yl)propyl]carbamoyl}anilino}pyrimidineYield 5.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4-Anilino-2-(4-carboxyanilino)-5-chloropyrimidine (Method 1; 170 mg, 0.5 mmol) was added to 1-(3-aminopropyl)imidazole (93.9 mg, 0.75 mmol) in a reaction tube. 1-Hydroxybenzotriazole (101 mg, 0.75 mmol) was added followed by N,N-diisopropylethylamine (130 mL 0.75 mmol) in DCM (4 ml). The mixture was flushed with argon and then stirred for 1 hour. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (105 mg, 0.55 mmol) in DCM (3 ml) was added and the mixture was stirred for 16 hours. The mixture was washed with saturated sodium bicarbonate solution (10 ml), water (10 ml) and saturated sodium chloride solution (10 ml), and the organic phase was loaded on a Varian Mega Bond Elut column. Elution with 0-10% 2.0M methanolic ammonia solution in DCM gave the product (11.6 mg, 5.2%). NMR: 2.0-2.15 (m, 2H), 3.0-3.1 (m, 2H), 4.25 (t, 2H), 7.25 (t, 1H), 7.4 (t, 2H), 7.6 (d, 4H), 7.7 (s, 1H), 7.75 (d, 2H), 7.85 (d, 1H), 8.3 (s, 1H), 8.6 (br t, 1H), 9.25 (d, 1H), 9.6 (br s, 1H), 10.3 (br s, 1H); LCMS (MH+): 448; HPLC (RT, System A): 6.16.

Workup

  1. customThe mixture was flushed with argon
  2. stirringthe mixture was stirred for 16 hours
  3. washThe mixture was washed with saturated sodium bicarbonate solution (10 ml), water (10 ml) and saturated sodium chloride solution (10 ml)
  4. washElution with 0-10% 2.0M methanolic ammonia solution in DCM

Sources & evidence

ORD record
ord-81b3dcd8767240a3875861bb63882bdc
Source dataset
uspto-grants-2003_11
Patent number
US06649608B2

Reaction notes

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