Ammonia → N-(3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine

HRID 1811841Notes

Reaction equation

HRID 1811841 reaction equation
F[C:2]1[C:7]([C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3C2CCCCO2)=[CH:6][CH:5]=[CH:4][N:3]=1.N[C:25]1[NH:26][C:27]2[C:32]([CH:33]=1)=[CH:31][CH:30]=[CH:29][CH:28]=2.Cl.[NH3:35]>CCO.CO>[CH3:17][C:15]1[N:14]=[C:13]2[C:9]([N:10]=[CH:11][NH:12]2)=[C:8]([C:7]2[C:2]([NH:35][C:31]3[C:32]4[CH:33]=[CH:25][NH:26][C:27]=4[CH:28]=[CH:29][CH:30]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)[N:16]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 1220741H-IndolamineHCID 595484686-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Product 1

HCID 178432534N-(3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amineYield 5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

6-(2-Fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (270 mg, 0.862 mmol) and 4 aminoindole (159.3 mg, 1.205 mmol) were suspended in EtOH (5.0 mL) and then aqueous hydrochloric acid, (5 N, 0.21 mL, 1.1 mmol) was added. The reaction flask was fit with a reflux condenser, placed in a preheated oil bath (100° C.), and stirred for 3 hours. Then, the reaction was cooled to room temperature, diluted with 2 N ammonia in MeOH (4.0 mL), and allowed to stand overnight. Then, the material was concentrated, treated with DMF and filtered. The solid was washed with DCM, and the filtrate was concentrated and purified on prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min). The fractions with product were collected, concentrated, and filtered through a silica gel plug (about 1 inch) with 10:1 DCM/2 N ammonia in MeOH to give N-(3-(2-methyl-9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine (13.7 mg, 5%). MS (ESI pos. ion) m/z 342 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 13.60 (s, 1H), 12.44 (s, 1H), 11.16 (s, 1H), 9.77 (d, J=7.04 Hz, 1H), 8.61 (s, 1H), 8.37 (dd, J=4.69 Hz, 1.76 Hz, 1H), 8.05 (dd, J=6.85 Hz, 1.56 Hz, 1H), 7.37 (t, J=2.64 Hz, 1H), 7.11-7.04 (m, 2H), 7.01 (dd, J=7.82 Hz, 4.69 Hz, 1H), 6.72 (s, 1H), 2.92 (s, 3H).

Workup

  1. customThe reaction flask was fit with a reflux condenser
  2. customplaced in a preheated oil bath
  3. temperatureThen, the reaction was cooled to room temperature
  4. waitto stand overnight
  5. concentrationThen, the material was concentrated
  6. additiontreated with DMF
  7. filtrationfiltered
  8. washThe solid was washed with DCM
  9. concentrationthe filtrate was concentrated
  10. custompurified on prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min)
  11. customThe fractions with product were collected
  12. concentrationconcentrated
  13. filtrationfiltered through a silica gel plug (about 1 inch) with 10:1 DCM/2 N ammonia in MeOH

Sources & evidence

ORD record
ord-326e8a6232404b13b03d6246577ee6c3
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

Loading…