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

HRID 75341Notes

Reaction equation

HRID 75341 reaction equation
[CH3:1][O:2][CH:3]1[CH2:6][N:5]([C:7]2[CH:8]=[C:9]3[N:18]([CH3:19])[CH:17]=[CH:16][C:10]3=[N:11][C:12]=2[C@@H:13]([NH2:15])[CH3:14])[CH2:4]1.[NH2:20][C:21]1[N:26]=[C:25]([NH2:27])[C:24]([C:28]#[N:29])=[C:23](Cl)[N:22]=1.C(N(C(C)C)C(C)C)C>C(#N)C>[NH2:20][C:21]1[N:26]=[C:25]([NH2:27])[C:24]([C:28]#[N:29])=[C:23]([NH:15][C@H:13]([C:12]2[N:11]=[C:10]3[CH:16]=[CH:17][N:18]([CH3:19])[C:9]3=[CH:8][C:7]=2[N:5]2[CH2:6][CH:3]([O:2][CH3:1])[CH2:4]2)[CH3:14])[N:22]=1

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 86707999(S)-1-(6-(3-Methoxyazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamineHCID 867080212,4-Diamino-6-chloropyrimidine-5-carbonitrile2×

Product 1

HCID 73055707(S)-2,4-Diamino-6-((1-(6-(3-methoxyazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)amino)pyrimidine-5-carbonitrileYield 15%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

(S)-1-(6-(3-Methoxyazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (469 mg, 1.80 mmol), 2,4-diamino-6-chloropyrimidine-5-carbonitrile (367 mg, 2.16 mmol), and N-ethyl-N-isopropylpropan-2-amine (628 μl, 3.60 mmol) were combined in acetonitrile (1.8 mL). The reaction mixture was heated in a microwave reactor at 120° C. for 2 hours. Additional 2,4-diamino-6-chloropyrimidine-5-carbonitrile (367 mg, 2.16 mmol) and N-ethyl-N-isopropylpropan-2-amine (628 μL, 3.60 mmol) were added. The reaction mixture was heated in a microwave reactor at 120° C. for 1 hour and then concentrated in vacuo. The residue was taken up in DMF and purified by preparative HPLC (basic mode) eluting with 25-50% ACN in water. The fractions containing the desired compound were combined and concentrated in vacuo. The residue was added to a silica gel column and was eluted with EtOAc. The fractions containing the desired product were combined and concentrated in vacuo to give the title compound as an off-white solid (106 mg, 15%). 1H NMR (500 MHz, CD3OD) δ ppm 1.49 (d, J=6.83 Hz, 3 H), 3.40 (s, 3 H), 3.70-3.74 (m, 1 H), 3.82 (s, 3 H), 3.89 (dd, J=7.32, 4.39 Hz, 1 H), 4.15-4.20 (m, 1 H), 4.32-4.40 (m, 2 H), 5.64 (q, J=6.83 Hz, 1 H), 6.51 (dd, J=3.42, 0.98 Hz, 1 H), 7.20 (s, 1 H), 7.31 (d, J=2.93 Hz, 1 H); ESI-MS m/z [M+H]+ calc'd for C19H23N9O, 394.2; found 394.5.

Workup

  1. temperatureThe reaction mixture was heated in a microwave reactor at 120° C. for 1 hour
  2. concentrationconcentrated in vacuo
  3. custompurified by preparative HPLC (basic mode)
  4. washeluting with 25-50% ACN in water
  5. additionThe fractions containing the desired compound
  6. concentrationconcentrated in vacuo
  7. additionThe residue was added to a silica gel column
  8. washwas eluted with EtOAc
  9. additionThe fractions containing the desired product
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0fce109c63da451ab0678a63d6bdfffa
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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