Hydrochloric Acid → HCID 178420797, compound

HRID 1811785Notes

Reaction equation

HRID 1811785 reaction equation
F[C:2]1[C:7]([C:8]2[N:16]=[CH:15][N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3C2CCCCO2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH:23]1[C:31]2[CH:30]=[CH:29][CH:28]=[C:27]([NH2:32])[C:26]=2[CH:25]=[CH:24]1.Cl>CCO.C(Cl)Cl.N.CO>[N:16]1[C:8]([C:7]2[C:2]([NH:32][C:27]3[C:26]4[CH:25]=[CH:24][NH:23][C:31]=4[CH:30]=[CH:29][CH:28]=3)=[N:3][CH:4]=[CH:5][CH:6]=2)=[C:9]2[C:13]([NH:12][CH:11]=[N:10]2)=[N:14][CH:15]=1

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 5834314-AminoindoleHCID 44479178HCID 44479178, compound

Product 1

HCID 178420797HCID 178420797, compoundYield 5.5%

Reagents, catalysts & solvents 4

HCID 222AmmoniaSolventHCID 702EthanolSolvent2×HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

6-(2-Fluoropyridin-3-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (115.0 mg, 0.3842 mmol) and 1H-indol-4-amine (Aldrich, St. Louis, Mo., 70.7 mg, 0.535 mmol) were suspended in EtOH (1.8 mL) and aqueous hydrochoric acid (5.0 M, 0.090 ml, 0.45 mmol) was added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.), and the reaction was stirred for 3 hours. Then, the reaction was cooled to room temperature and diluted with DCM, 2 N ammonia in MeOH, EtOH, and MeOH and concentrated. The residue was treated with MeOH and filtered. Neither the filtrate nor the solid contained pure material, so they were combined, concentrated, treated with DMF, and filtered. The filtrate was concentrated and purified on 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, 50:1 DCM/2 N ammonia in MeOH to 20:1 DCM/2 N ammonia in MeOH to 5:1 DCM/2 N ammonia in MeOH) to afford N-(3-(9H-purin-6-yl)pyridin-2-yl)-1H-indol-4-amine (6.9 mg, 5% yield). MS (ESI pos. ion) m/z: 328, (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 12.90 (s, 1H), 11.16 (s, 1H), 9.87 (d, J=7.82 Hz, 1H), 9.24 (s, 1H), 8.73 (s, 1H), 8.43 (dd, J=4.69 Hz, 1.96 Hz, 1H), 8.28 (dd, J=4.6 Hz, 3.81 Hz, 1H), 7.38-7.35 (m, 1H), 7.09 (s, 1H), 7.08-7.06 (m, 1H), 7.04 (dd, J=7.82 Hz, 4.69 Hz, 1H), 6.79-6.76 (m, 1H).

Workup

  1. customThe flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. temperatureThen, the reaction was cooled to room temperature
  4. concentrationconcentrated
  5. additionThe residue was treated with MeOH
  6. filtrationfiltered
  7. concentrationconcentrated
  8. additiontreated with DMF
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. custompurified on HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min)
  12. customThe fractions with product were collected
  13. concentrationconcentrated
  14. filtrationfiltered through a silica gel plug (about 1 inch, 50:1 DCM/2 N ammonia in MeOH to 20:1 DCM/2 N ammonia in MeOH to 5:1 DCM/2 N ammonia in MeOH)

Sources & evidence

ORD record
ord-0c77fda62e6646f2989f662198bc7272
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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