Ammonia → HCID 49784990, compound

HRID 1621402Notes

Reaction equation

HRID 1621402 reaction equation
[NH3:1].CC(O)C.[CH3:6][C:7]1[N:12]=[C:11](SC)[N:10]=[C:9]([C:15]2[C:16]([NH:32][C:33]3[C:34]4[CH:35]=[N:36][N:37](C5CCCCO5)[C:38]=4[CH:39]=[CH:40][CH:41]=3)=[N:17][CH:18]=[C:19]([CH2:21][N:22]3[CH2:27][CH2:26][N:25]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:24][CH2:23]3)[CH:20]=2)[N:8]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl.CO>[NH2:1][C:11]1[N:12]=[C:7]([CH3:6])[N:8]=[C:9]([C:15]2[C:16]([NH:32][C:33]3[C:34]4[CH:35]=[N:36][NH:37][C:38]=4[CH:39]=[CH:40][CH:41]=3)=[N:17][CH:18]=[C:19]([CH2:21][N:22]3[CH2:23][CH2:24][N:25]([S:28]([CH3:31])(=[O:29])=[O:30])[CH2:26][CH2:27]3)[CH:20]=2)[N:10]=1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 3776IsopropanolHCID 6422Trifluoroacetic acidHCID 66611529HCID 66611529, compound

Product 1

HCID 49784990HCID 49784990, compoundYield 22.88%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
90 °C

Procedure

2 M NH3 in 2-propanol (2.00 mL, 92 mmol) was added to N-(3-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-4-amine (97 mg, 0.159 mmol) and the mixture was sealed and heated at 90° C. overnight. After cooling, the precipitate was collected and dried to give a yellow solid which was dissolved in DCM (3.00 mL, 46.6 mmol) and then TFA (1.50 mL, 19.47 mmol) was slowly added. The mixture was stirred at rt for 1 h and then concentrated, adsorbed onto a plug of silica gel and chromatographed through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (DCM to 10% MeOH in DCM) to give N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-yl)-1H-indazol-4-amine (18 mg, 0.036 mmol, 22.88% yield) as a yellow solid. LCMS (API-ES) m/z 495 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ 13.10 (br. s., 1H) 12.27 (s, 1H) 8.75 (s, 1H) 8.32 (br. s., 1H) 8.19 (s, 1H) 8.13 (d, J=7.04 Hz, 1H) 7.78 (br. s., 2H) 7.31 (t, J=8.31 Hz, 1H) 7.15 (d, J=8.22 Hz, 1H) 3.53 (s, 2H) 3.12 (br. s., 4H) 2.87 (s, 3H) 2.57 (s, 3H) 2.37-2.49 (m, 4H).

Workup

  1. customthe mixture was sealed
  2. temperatureAfter cooling
  3. customthe precipitate was collected
  4. customdried
  5. customto give a yellow solid which
  6. concentrationconcentrated
  7. customchromatographed through a RediSep®, Teledyne ISCO, Lincoln, Nebr

Sources & evidence

ORD record
ord-a7ec42890bb0419794ec7b129ad49144
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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