Triethylamine → 4-N-(3-bromophenyl)-7-N-methylpyrido[4,3-d]pyrimidine-4,7-diamine

HRID 50799Notes

Reaction equation

HRID 50799 reaction equation
F[C:2]1[N:11]=[CH:10][C:9]2[C:8]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:6]=[N:5][C:4]=2[CH:3]=1.[CH2:20]([N:22](CC)CC)C.Cl.CN>C(O)(C)C>[Br:19][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[NH:12][C:8]1[C:9]2[CH:10]=[N:11][C:2]([NH:22][CH3:20])=[CH:3][C:4]=2[N:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 5328251N-(3-bromophenyl)-7-fluoropyrido[4,3-d]pyrimidin-4-amineHCID 6364545Methylamine hydrochloride

Product 1

HCID 53282524-N-(3-bromophenyl)-7-N-methylpyrido[4,3-d]pyrimidine-4,7-diamineYield 65.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 7-fluoro-4-(3-bromoanilino)-pyrido[4,3-d]pyrimidine (74 mg, 0.23 mmol), triethylamine (7 mL, 50 mmol) and methylamine hydrochloride (3.0 g, 44 mmol) in isopropanol (30 mL) contained in a steel bomb is stirred at 95° C. (oil bath) for 5 h. The resulting mixture is concentrated under vacuum, basified with aqueous Na2CO3, diluted with water and extracted with EtOAc (3×100 mL). Chromatography of this extract on silica gel (3% MeOH/CH2Cl2) gives 4-(3-bromoanilino)-7-methylaminopyrido[4,3-d]pyrimidine (50 mg, 65%) as a pale yellow solid. 1H NMR (DMSO) δ 9.93 (1H, brs), 9.37 (1H, s), 8.47 (1H, s), 8.18 (1H, s), 7.84 (1H, d, J=7.8 Hz), 7.34 (1H, t, J=7.9 Hz), 7.30 (1H, brd, J=8.1 Hz), 7.19 (1H, q, J=4.7 Hz), 6.35 (1H, s), 2.85 (3H, d, J=4.8 Hz)

Workup

  1. concentrationThe resulting mixture is concentrated under vacuum
  2. additiondiluted with water
  3. extractionextracted with EtOAc (3×100 mL)
  4. extractionChromatography of this extract on silica gel (3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-396ec8a473cd4871aec6dc5efc65b446
Source dataset
uspto-grants-2004_03
Patent number
US06713484B2

Reaction notes

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