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

HRID 75327Notes

Reaction equation

HRID 75327 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](Cl)[C:25]([C:29]#[N:30])=[C:24]([CH3:31])[N:23]=1.C(N(C(C)C)C(C)C)C>C(#N)C>[NH2:21][C:22]1[N:23]=[C:24]([CH3:31])[C:25]([C:29]#[N:30])=[C:26]([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:27]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 754124462-Amino-4-chloro-6-methyl-5-pyrimidinecarbonitrileHCID 86708019(S)-1-(1-methyl-6-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochloride

Product 1

HCID 73055110(S)-2-Amino-4-methyl-6-((1-(1-methyl-6-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrileYield 29%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

(S)-1-(1-Methyl-6-(pyridin-2-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochloride (151 mg, 0.522 mmol), 2-amino-4-chloro-6-methylpyrimidine-5-carbonitrile (80 mg, 0.475 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.248 mL, 1.42 mmol) were combined in acetonitrile (6 mL). The reaction mixture was heated in a microwave reactor at 120° C. for 2 hours and then concentrated. The residue was taken up in DMF and purified by preparative HPLC (basic mode) eluting with 20-35% ACN in water. The fractions containing the desired compound were combined and concentrated in vacuo. The residue was taken up in DMF and further purified by preparative HPLC (acid mode) eluting with 1-25% ACN in water. The fractions containing the desired compound were combined, neutralized with NaHCO3, and extracted with EtOAc (200 mL). The organic layers were combined, dried over Na2SO4, and concentrated in vacuo to give the title compound (53 mg, 29%). 1H NMR (500 MHz, CD3OD) δ ppm 1.34-1.41 (m, 3 H), 2.31 (d, J=1.46 Hz, 3 H), 3.88 (d, J=1.46 Hz, 3H), 5.68-5.79 (m, 1 H), 6.67 (d, J=2.44 Hz, 1 H), 7.47 (dd, J=7.32, 4.88 Hz, 1 H), 7.58-7.61 (m, 1 H), 7.67 (d, J=7.81 Hz, 1 H), 7.86 (s, 1 H), 7.99 (t, J=7.81 Hz, 1 H), 8.68-8.73 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C21H20N8, 385; found 385.

Workup

  1. concentrationconcentrated
  2. custompurified by preparative HPLC (basic mode)
  3. washeluting with 20-35% ACN in water
  4. additionThe fractions containing the desired compound
  5. concentrationconcentrated in vacuo
  6. customfurther purified by preparative HPLC (acid mode)
  7. washeluting with 1-25% ACN in water
  8. additionThe fractions containing the desired compound
  9. extractionextracted with EtOAc (200 mL)
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-712fe435f6cd4f7aa83368759abe12f5
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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