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

HRID 75320Notes

Reaction equation

HRID 75320 reaction equation
Cl.[CH3:2][N:3]1[C:11]2[C:6](=[N:7][C:8]([C@@H:18]([NH2:20])[CH3:19])=[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[CH:10]=2)[CH:5]=[CH:4]1.[NH2:21][C:22]1[N:27]=[C:26]([NH2:28])[C:25]([C:29]#[N:30])=[C:24](Cl)[N:23]=1.C(N(C(C)C)C(C)C)C>C(#N)C>[NH2:21][C:22]1[N:27]=[C:26]([NH2:28])[C:25]([C:29]#[N:30])=[C:24]([NH:20][C@H:18]([C:8]2[N:7]=[C:6]3[CH:5]=[CH:4][N:3]([CH3:2])[C:11]3=[CH:10][C:9]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH3:19])[N:23]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86708019(S)-1-(1-methyl-6-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochlorideHCID 867080212,4-Diamino-6-chloropyrimidine-5-carbonitrile

Product 1

HCID 73054564(S)-2,4-Diamino-6-((1-(1-methyl-6-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of (S)-1-(1-methyl-6-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochloride (50 mg, 0.198 mmol), 2,4-diamino-6-chloropyrimidine-5-carbonitrile (50.4 mg, 0.297 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.104 mL, 0.594 mmol) in acetonitrile (6 mL), was heated in a microwave reactor at 120° C. for 2 hours. After cooling to room temperature, the reaction mixture was concentrated, re-dissolved in DMF, and purified by preparative HPLC (basic mode) using a 20-30% CH3CN gradient in H2O. The desired fractions were combined and solvent was removed in vacuo. The residue was purified again by preparative HPLC (basic mode) using a 25-35% CH3CN gradient in H2O. The pure fractions were combined and the solvent was removed in vacuo to give the title compound as a colorless film (24 mg, 31%). 1H NMR (500 MHz, CD3OD) δ ppm 1.59 (d, J=7.32 Hz, 3 H), 4.04 (br s, 3 H), 5.84 (q, J=7.32 Hz, 1 H), 6.88 (d, J=3.42 Hz, 1 H), 7.62-7.68 (m, 1 H), 7.90 (d, J=7.81 Hz, 1 H), 8.08 (d, J=2.93 Hz, 1 H), 8.16 (td, J=7.81, 1.95 Hz, 1H), 8.66 (s, 1H), 8.83 (d, J=4.88 Hz, 1H). ESI-MS m/z [M+H]+ calc'd for C20H19N9, 386. found 386.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. dissolutionre-dissolved in DMF
  3. custompurified by preparative HPLC (basic mode)
  4. customsolvent was removed in vacuo
  5. customThe residue was purified again by preparative HPLC (basic mode)
  6. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-b594b7afca0b4b8aa815cf4b94be9967
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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