Diisopropylethylamine → (S)-5-Chloro-N4-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)pyrimidine-2,4,6-triamine

HRID 75335Notes

Reaction equation

HRID 75335 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[N:16]([CH3:17])[N:15]=[CH:14][CH:13]=3)[CH:10]=2)[CH:5]=[CH:4]1.[Cl:21][C:22]1[C:23]([NH2:30])=[N:24][C:25]([NH2:29])=[N:26][C:27]=1Cl.C(N(C(C)C)C(C)C)C>C(#N)C>[Cl:21][C:22]1[C:27]([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[N:16]([CH3:17])[N:15]=[CH:14][CH:13]=2)[CH3:19])=[N:26][C:25]([NH2:29])=[N:24][C:23]=1[NH2:30]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 3456315,6-Dichloro-2,4-pyrimidinediamineHCID 86708027(S)-1-(1-Methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochloride

Product 1

HCID 73055401(S)-5-Chloro-N4-(1-(1-methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)pyrimidine-2,4,6-triamineYield 14.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

(S)-1-(1-Methyl-6-(1-methyl-1H-pyrazol-5-yl)-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine hydrochloride (95 mg, 0.372 mmol), 5,6-dichloropyrimidine-2,4-diamine (100 mg, 0.559 mmol), and N-ethyl-N-isopropylpropan-2-amine (0.20 mL, 1.1 mmol) were combined in acetonitrile (6 mL). The reaction mixture was heated in a microwave reactor at 120° C. for 2 hours and then at 160° C. for 1.5 hours. The mixture was concentrated. The residue was taken up in DMF and purified by preparative HPLC (basic mode) eluting with 30% ACN in water. The fractions containing the desired compound were combined and extracted with EtOAc (200 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo to give the title compound (21 mg, 14%). 1H NMR (500 MHz, CD3OD) δ ppm 1.38 (d, J=6.35 Hz, 3 H), 3.65 (s, 3 H), 3.83-3.89 (m, 3 H), 5.38 (q, J=6.67 Hz, 1 H), 6.40-6.46 (m, 1 H), 6.65-6.70 (m, 1 H), 7.58-7.64 (m, 2 H), 7.80 (s, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H20ClN9, 398; found 398.

Workup

  1. concentrationThe mixture was concentrated
  2. custompurified by preparative HPLC (basic mode)
  3. washeluting with 30% ACN in water
  4. additionThe fractions containing the desired compound
  5. extractionextracted with EtOAc (200 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e26e3b9099344d148a6064e75fd998e2
Source dataset
uspto-grants-2014_09
Patent number
US08835420B2

Reaction notes

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