4-Pyrimidinecarboxylic acid → HCID 66801975, compound

HRID 528055

Reaction equation

HRID 528055 reaction equation
[NH2:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=4[NH:18][C:17]3=[O:25])[CH2:12][CH2:11]2)=[N:4][CH:5]=[N:6][C:7]=1[NH:8][CH3:9].CN(C(O[N:34]1N=N[C:36]2[CH:37]=[CH:38][CH:39]=[N:40][C:35]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1C=CC(C(O)=O)=NC=1>CC(N(C)C)=O.C(N(C(C)C)CC)(C)C>[CH3:9][N:8]1[C:36]([C:37]2[CH:38]=[CH:39][N:40]=[CH:35][N:34]=2)=[N:1][C:2]2[C:7]1=[N:6][CH:5]=[N:4][C:3]=2[N:10]1[CH2:11][CH2:12][CH:13]([N:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[NH:18][C:17]2=[O:25])[CH2:14][CH2:15]1

Participants

6

Reactant 3

HCID 1693064-Pyrimidinecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66802269HCID 66802269, compound

Product 1

HCID 66801975HCID 66801975, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 31374DimethylacetamideSolventHCID 81531DiisopropylethylamineSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 1-(1-(5-amino-6-(methylamino)pyrimidin-4-yl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one (50 mg, 0.14 mmol) in anhydrous DMA (5 mL) and diisopropylethylamine (0.5 mL) were added HATU (150 mg, 0.39 mmol), and pyrimidine-4-carboxylic acid (100 mg, 0.8 mmol). The reaction mixture was stirred for 1 h, and concentrated under reduced pressure. The resulting oil was dissolved in 10 mL of dichloromethane, and the solution was washed with 5 mL of water. The organic layer was dried over MgSO4, concentrated under reduced pressure, and the residue was dissolved in Acetic acid (2 mL). The reaction mixture was heated in a microwave reactor to 150° C. for 20 min, and concentrated under reduced pressure. The product was purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid) to give 3 mg of the title compound. 1H NMR (400 MHz, DMSO-d6): δ 10.85 (s, 1H), 9.34 (s, 1H), 8.96 (d, 1H), 8.36 (s, 1H), 8.27 (d, 1H), 7.21-7.14 (m, 1H), 6.93 (d, 3H), 4.64-4.52 (m, 1H), 4.18 (s, 3H), 2.37 (dd, 2H), 1.85 (t, 2H); MS (EI) for C23H21N9O: 428.4 (MH+).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe resulting oil was dissolved in 10 mL of dichloromethane
  3. washthe solution was washed with 5 mL of water
  4. dry with materialThe organic layer was dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. dissolutionthe residue was dissolved in Acetic acid (2 mL)
  7. concentrationconcentrated under reduced pressure
  8. customThe product was purified by preparatory HPLC (reverse-phase, acetonitrile/water with 0.1% formic acid)

Sources & evidence

ORD record
ord-aaf78d41a2c94ac181a12b073d4a929b
Source dataset
uspto-grants-2016_05
Patent number
US09346807B2

Linked notes

Loading…