2-Amino-4-chloro-6-methylpyrimidine → HCID 86653034, compound

HRID 1948744

Reaction equation

HRID 1948744 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:8]([CH:18]=O)=[CH:7]2.Cl.CN.C[CH2:24][N:25](C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[NH2:45][C:46]1[N:51]=[C:50](Cl)[CH:49]=[C:48]([CH3:53])[N:47]=1>C(Cl)Cl.C1COCC1>[CH3:24][N:25]([CH2:18][C:8]1[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[N:10][C:11]2[C:6]([CH:7]=1)=[CH:5][CH:4]=[CH:3][C:2]=2[CH3:1])[C:50]1[CH:49]=[C:48]([CH3:53])[N:47]=[C:46]([NH2:45])[N:51]=1

Participants

8

Reactant 5

HCID 218102-Amino-4-chloro-6-methylpyrimidineHCID 81531Diisopropylethylamine2×HCID 8336808-Methyl-2-phenylquinoline-3-carboxaldehydeHCID 2724942TriacetoxyborohydrideHCID 6364545Methylamine hydrochloride

Product 1

HCID 86653034HCID 86653034, compoundYield 20.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 8-methyl-2-phenylquinoline-3-carboxaldehyde (100 mg, 0.4 mmol), methylamine hydrochloride (120 mg, 1.8 mmol) and DIPEA (230 mg, 1.8 mmol) in DCM (20 mL) was treated with titanium(IV) n-propoxide (228 mg, 0.8 mmol). The reaction mixture was stirred at r.t. for 18 h. The solvent was removed in vacuo and the residue dissolved in THF (20 mL) before triacetoxyborohydride (170 mg, 0.8 mmol) was added. The reaction mixture was stirred at r.t. for 2 h, the solvent removed in vacuo and the residue partitioned between DCM (100 mL) and water (30 mL). The organic layer was separated, dried (MgSO4) and the solvent removed in vacuo. The residue was dissolved in NMP (2 mL) and to this solution was added DIPEA (230 mg, 1.8 mmol) and 2-amino-4-chloro-6-methylpyrimidine (57 mg, 0.4 mmol). The mixture was heated in a microwave at 220° C. for 2 h. Purification by preparative HPLC (Method 1) gave the title compound as an off-white solid (30 mg, 20%). δH (CDCl3) 7.82 (s, 1H), 7.62-7.70 (m, 2H), 7.61 (d, J 7.9 Hz, 1H), 7.46-7.55 (m, 5H), 5.75 (s, 1H), 4.93 (s, 2H), 4.67 (s, 2H), 2.93 (s, 3H), 2.82 (s, 3H), 2.22 (s, 3H). LCMS (ES+) 370.2 (M+H)+, RT 2.36 minutes (Method 3).

Workup

  1. customThe solvent was removed in vacuo
  2. additionwas added
  3. stirringThe reaction mixture was stirred at r.t. for 2 h
  4. customthe solvent removed in vacuo
  5. customthe residue partitioned between DCM (100 mL) and water (30 mL)
  6. customThe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed in vacuo
  9. dissolutionThe residue was dissolved in NMP (2 mL) and to this solution
  10. temperatureThe mixture was heated in a microwave at 220° C. for 2 h
  11. customPurification by preparative HPLC (Method 1)

Sources & evidence

ORD record
ord-99bafe0f00184fe1b4e7347d3607d504
Source dataset
uspto-grants-2013_03
Patent number
US08399483B2

Linked notes

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