Hydrogen Bromide → HCID 17981142, compound

HRID 347760Notes

Reaction equation

HRID 347760 reaction equation
[F:1][C:2]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:3]=1[NH:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7](Cl)[N:6]=1.Br.C(Cl)Cl.[O:21]1[CH2:26][CH2:25][N:24]([CH2:27][CH2:28][CH2:29][O:30][C:31]2[CH:37]=[CH:36][C:34]([NH2:35])=[CH:33][CH:32]=2)[CH2:23][CH2:22]1>CN1C(=O)CCC1>[F:1][C:2]1[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][C:3]=1[NH:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([NH:35][C:34]2[CH:36]=[CH:37][C:31]([O:30][CH2:29][CH2:28][CH2:27][N:24]3[CH2:23][CH2:22][O:21][CH2:26][CH2:25]3)=[CH:32][CH:33]=2)[N:6]=1

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 6344DichloromethaneHCID 17981132HCID 17981132, compoundHCID 220609034-(3-Morpholinopropoxy)aniline

Product 1

HCID 17981142HCID 17981142, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-(2-Fluoro-5-methylanilino)-2-chloropyrimidine (Reference Example A-10, 140 mg, 0.6 mmol) was dissolved in dry NMP (2 ml) and 4-(3-morpholinopropoxy)aniline.2.HBr salt (see CAS Registry No. 100800–40–6; J.Am.Chem.Soc., 76, 1954, 4396; 188 mg, 0.5 mmol) added. The mixture was stirred at ambient temperature for 5 minutes, then checked to ensure the reaction mixture was acidic (pH 1) and heated at 100° C. for 3 hours. The mixture was allowed to cool and evaporated to dryness to give an oil. Silica (2 g) and DCM (10 ml) were added and the mixture then re-evaporated to dryness and purified by chromatography on a Mega Bond Elute column (10 g) (eluting with DCM (2×25 ml), 2% NH3 in MeOH (3×25 ml), 4% NH3 in MeOH (3×25 ml), 6% NH3 in MeOH (3×25 ml), 10% NH3 in MeOH (9×25 ml)) to give the title product as a colourless oil, which was triturated with diethyl ether to give a white solid (95 mg, 46%). NMR (300 MHz): 1.8 (m, 2H), 2.2 (s, 3H), 2.4 (m, 4H), 2.4 (m, 2H), 3.6 (t, 3H), 3.9 (t, 2H), 6.2 (d, 1H), 6.8 (d, 2H), 6.9 (m, 1H), 7.1 (m, 1H), 7.5 (d, 2H), 7.8 (d, 1H), 8.0 (d, 1H), 8.9 (s, 2H); m/z: (ES+) 438.2 (MH+).

Workup

  1. addition188 mg, 0.5 mmol) added
  2. temperatureheated at 100° C. for 3 hours
  3. temperatureto cool
  4. customevaporated to dryness
  5. customto give an oil
  6. customthe mixture then re-evaporated to dryness
  7. custompurified by chromatography on a Mega Bond
  8. washElute
  9. washcolumn (10 g) (eluting with DCM (2×25 ml), 2% NH3 in MeOH (3×25 ml), 4% NH3 in MeOH (3×25 ml), 6% NH3 in MeOH (3×25 ml), 10% NH3 in MeOH (9×25 ml))

Sources & evidence

ORD record
ord-6529bb273aed4a49ad32975e6bc0b0e3
Source dataset
uspto-grants-2007_02
Patent number
US07176212B2

Reaction notes

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