Diisopropylethylamine → (S)-N6-(1-(6-(1-(Difluoromethyl)-1H-pyrazol-5-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)-9H-purine-2,6-diamine

HRID 75337Notes

Reaction equation

HRID 75337 reaction equation
[F:1][CH:2]([F:21])[N:3]1[C:7]([C:8]2[CH:9]=[C:10]3[N:19]([CH3:20])[CH:18]=[CH:17][C:11]3=[N:12][C:13]=2[C@@H:14]([NH2:16])[CH3:15])=[CH:6][CH:5]=[N:4]1.Cl[C:23]1[N:31]=[C:30]([NH2:32])[N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][NH:27]2.C(N(C(C)C)C(C)C)C>C(#N)C>[F:21][CH:2]([F:1])[N:3]1[C:7]([C:8]2[CH:9]=[C:10]3[N:19]([CH3:20])[CH:18]=[CH:17][C:11]3=[N:12][C:13]=2[C@@H:14]([NH:16][C:23]2[N:31]=[C:30]([NH2:32])[N:29]=[C:28]3[C:24]=2[N:25]=[CH:26][NH:27]3)[CH3:15])=[CH:6][CH:5]=[N:4]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 86707995(S)-1-(6-(1-(Difluoromethyl)-1H-pyrazol-5-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamineHCID 1785084356-chloro-1H-purin-2-amine

Product 1

HCID 178461978(S)-N6-(1-(6-(1-(Difluoromethyl)-1H-pyrazol-5-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)-9H-purine-2,6-diamine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

(S)-1-(6-(1-(Difluoromethyl)-1H-pyrazol-5-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (172 mg, 0.590 mmol), 6-chloro-9H-purin-2-amine (100 mg, 0.590 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.31 mL, 1.8 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 was purified by preparative HPLC (acid mode) eluting with 5-20% ACN in water. The fractions containing the desired compound were combined and concentrated in vacuo. The residue was further purified by preparative HPLC (basic mode) eluting with 25-35% ACN in water. The fractions containing the desired product were combined and concentrated in vacuo to give the title compound as a white solid. 1H NMR (500 MHz, CD3OD) δ ppm 1.58 (d, J=6.83 Hz, 3 H), 3.87 (s, 3 H), 5.94-6.01 (m, 1 H), 6.64 (d, J=2.93 Hz, 1 H), 6.87 (d, J=2.44 Hz, 1 H), 7.46-7.76 (m, 2 H), 7.93 (s, 1 H), 8.18 (s, 1 H); ESI-MS m/z [M+H]+ calc'd for C19H18F2N10, 425; found 425.

Workup

  1. concentrationconcentrated
  2. customwas purified by preparative HPLC (acid mode)
  3. washeluting with 5-20% ACN in water
  4. additionThe fractions containing the desired compound
  5. concentrationconcentrated in vacuo
  6. customThe residue was further purified by preparative HPLC (basic mode)
  7. washeluting with 25-35% ACN in water
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-82174ae1692547bfa85183216b6ed44c
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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