Hydrochloric Acid → HCID 178463549, compound

HRID 510916Notes

Reaction equation

HRID 510916 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11](C(OCC)C)[CH:12]=2)[C:5]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)=[C:4]([CH:26]([NH2:28])[CH3:27])[CH:3]=1.Br[C:30]1[N:38]=[CH:37][N:36]=[C:35]2[C:31]=1[N:32]=[CH:33][N:34]2C1CCCCO1.C(N(CC)C(C)C)(C)C.Cl.O>C(O)C.CO>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:12]=[N:11][NH:10][CH:9]=2)[C:5]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)=[C:4]([CH:26]([NH:28][C:30]2[N:38]=[CH:37][N:36]=[C:35]3[C:31]=2[N:32]=[CH:33][NH:34]3)[CH3:27])[CH:3]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 81531DiisopropylethylamineHCID 58368616HCID 58368616, compoundHCID 679691831-{4-Chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3',5'-difluorobiphenyl-2-yl}ethanamine

Product 1

HCID 178463549HCID 178463549, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 887MethanolSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 1-{4-chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3′,5′-difluorobiphenyl-2-yl}ethanamine (60 mg, 0.15 mmol), 6-bromo-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (63 mg, 0.22 mmol, from Example 108, Step 1), and N,N-diisopropylethylamine (77 μL, 0.44 mmol) in ethanol (2.8 mL) was heated in the microwave at 130° C. for 30 minutes. Alternatively, this reaction can be heated at 90° C. overnight on the benchtop. The reaction mixture was cooled to room temperature, treated with 6 M Hydrogen chloride in water (0.49 mL, 3.0 mmol), and stirred for 30 minutes. The reaction mixture was diluted slightly with methanol, filtered, and directly purified via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (29 mg, 43%). LCMS for C22H17ClF2N7 (M+H)+: m/z=452.1. Found: 452.0; 1H NMR (300 MHz, DMSO-d6): δ 12.8 (br s, 1H), 8.32-8.23 (m, 1H), 8.11 (s, 1H), 8.06 (s, 1H), 7.65 (s, 1H), 7.46 (s, 1H), 7.36-7.23 (m, 3H), 7.09-7.01 (m, 1H), 6.96 (d, J=8.5 Hz, 1H), 5.09-4.96 (m, 1H), 1.34 (d, J=6.7 Hz, 3H).

Workup

  1. customAlternatively, this reaction
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationfiltered
  4. customdirectly purified via preparative LCMS (XBridge C18 column
  5. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-4a3e0c9f292846f7ba9aa5d56b5f2b12
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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