Triethylamine → 4-[2-[(5-Bromopyridin-3-yl)acetyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine

HRID 449462

Reaction equation

HRID 449462 reaction equation
C(N(CC)CC)C.Cl.Cl.Cl.[CH3:11][N:12]1[CH2:17][CH2:16][N:15]([C:18]2[CH:23]=[C:22]([C:24]3[CH:33]=[C:32]4[C:27]([CH2:28][CH2:29][NH:30][CH2:31]4)=[CH:26][CH:25]=3)[N:21]=[C:20]([NH2:34])[N:19]=2)[CH2:14][CH2:13]1.[Br:35][C:36]1[CH:37]=[C:38]([CH2:42][C:43](O)=[O:44])[CH:39]=[N:40][CH:41]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>O>[Br:35][C:36]1[CH:37]=[C:38]([CH2:42][C:43]([N:30]2[CH2:29][CH2:28][C:27]3[C:32](=[CH:33][C:24]([C:22]4[CH:23]=[C:18]([N:15]5[CH2:14][CH2:13][N:12]([CH3:11])[CH2:17][CH2:16]5)[N:19]=[C:20]([NH2:34])[N:21]=4)=[CH:25][CH:26]=3)[CH2:31]2)=[O:44])[CH:39]=[N:40][CH:41]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 28025392-(5-Bromopyridin-3-yl)acetic acidHCID 675428394-(4-Methylpiperazin-1-yl)-6-(1,2,3,4-tetrahydroisoquinolin-7-yl)pyrimidin-2-amine trihydrochloride

Product 1

HCID 594965344-[2-[(5-Bromopyridin-3-yl)acetyl]-1,2,3,4-tetrahydroisoquinolin-7-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Triethylamine (16 uL, 0.12 mmol) was added to a mixture of 4-(4-methylpiperazin-1-yl)-6-(1,2,3,4-tetrahydroisoquinolin-7-yl)pyrimidin-2-amine trihydrochloride (50 mg, 0.1 mmol), (5-bromopyridin-3-yl)acetic acid (30.0 mg, 0.14 mmol) (Lancaster, Cat. #L13579), and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (56 mg, 0.13 mmol) in N,N-dimethylformate (1.5 mL). The reaction mixture was stirred at r.t. overnight. The mixture was diluted with water, and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with MeOH in dichloromethane (0-10%) to afford the desired product. Analytic LCMS (M+H)+: m/z=521.95/523.95.

Workup

  1. extractionextracted with ethyl acetate (3×10 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column with MeOH in dichloromethane (0-10%)

Sources & evidence

ORD record
ord-162194c84b7840e29aa116013401c182
Source dataset
uspto-grants-2013_07
Patent number
US08481732B2

Linked notes

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