Triethylamine → (R)-2,4-Diamino-6-((1-(1-methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrile

HRID 75344Notes

Reaction equation

HRID 75344 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[N:6][C:7]([C@H:17]([NH2:19])[CH3:18])=[C:8]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH:9]=2)[CH:4]=[CH:3]1.[NH2:20][C:21]1[N:26]=[C:25]([NH2:27])[C:24]([C:28]#[N:29])=[C:23](Cl)[N:22]=1.CCN(CC)CC.C(=O)(O)[O-].[Na+]>CN(C=O)C>[NH2:20][C:21]1[N:26]=[C:25]([NH2:27])[C:24]([C:28]#[N:29])=[C:23]([NH:19][C@@H:17]([C:7]2[N:6]=[C:5]3[CH:4]=[CH:3][N:2]([CH3:1])[C:10]3=[CH:9][C:8]=2[N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[CH3:18])[N:22]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 86708016(R)-1-(1-Methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethan-1-amineHCID 867080212,4-Diamino-6-chloropyrimidine-5-carbonitrile

Product 1

HCID 73056003(R)-2,4-Diamino-6-((1-(1-methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrileYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a 50 mL pear flask were added (R)-1-(1-methyl-6-morpholino-1H-pyrrolo[3,2-b]pyridin-5-yl)ethan-1-amine (0.5 g, 1.921 mmol) and 2,4-diamino-6-chloropyrimidine-5-carbonitrile (0.326 g, 1.92 mmol) in DMF (9.60 mL) to give a white suspension. To the suspension was added Et3N (0.535 mL, 3.84 mmol) and the mixture was stirred at 100° C. for 6 hours. The mixture was allowed to stand at RT overnight. Saturated aqueous sodium bicarbonate solution (100 mL) was added, and the mixture was extracted with EtOAc (3×). The organic layers were combined, dried over MgSO4, filtered, and concentrated. The damp residue was slurried in Et2O. The solids were collected on a fritted glass funnel and washed with Et2O. UPLC indicated the presence of a small impurity having a slightly shorter retention time than the desired product. The solids were dissolved in hot EtOH and recrystallized overnight to give the title compound as an off-white solid (340 mg, 45.0%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.39 (d, J=6.32 Hz, 3 H), 2.70-2.83 (m, 2 H), 3.05 (br s, 2 H), 3.72-3.91 (m, 7 H), 5.90 (quin, J=6.76 Hz, 1 H), 6.41 (s, 2 H), 6.45-6.53 (m, 2 H), 6.58 (s, 2 H), 7.51-7.61 (m, 1 H), 7.84 (s, 1 H); ESI-MS m/z [M+H]+ calc'd for C19H23N9O, 394; found 394.

Workup

  1. customto give a white suspension
  2. waitto stand at RT overnight
  3. extractionthe mixture was extracted with EtOAc (3×)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe solids were collected on a fritted glass funnel
  8. washwashed with Et2O
  9. dissolutionThe solids were dissolved in hot EtOH
  10. customrecrystallized overnight

Sources & evidence

ORD record
ord-716c0141aea14cf999ed256a0cb20887
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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