Triethylamine → HCID 66995319, compound

HRID 2066427Notes

Reaction equation

HRID 2066427 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]4[CH:21]=[CH:20][C:19]([CH2:22][NH2:23])=[CH:18][CH:17]=4)=[CH:13][CH:14]=3)[NH:9][N:8]=2)[CH:4]=[N:3]1.C(N(CC)CC)C.[F:31][C:32]1[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=1)[C:35](Cl)=[O:36]>O1CCCC1>[F:31][C:32]1[CH:33]=[C:34]([CH:38]=[CH:39][CH:40]=1)[C:35]([NH:23][CH2:22][C:19]1[CH:20]=[CH:21][C:16]([C:12]2[CH:11]=[C:10]3[C:15]([C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)=[N:8][NH:9]3)=[CH:14][CH:13]=2)=[CH:17][CH:18]=1)=[O:36]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 743763-Fluorobenzoyl chlorideHCID 66995212HCID 66995212, compound

Product 1

HCID 66995319HCID 66995319, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 0° C. suspension of Example 31B (70 mg, 0.231 mmol) in tetrahydrofuran (15 ml) was treated with triethylamine (1.00 ml, 7.17 mmol) followed by 3-fluorobenzoyl chloride (0.014 ml, 0.115 mmol) added dropwise. The reaction was allowed to warm to room temperature slowly and after 2 hours was treated with an additional 14 uL acid chloride, stirred for 18 hours, then partitioned between brine and ethyl acetate. The organic extract was dried with MgSO4, concentrated and the residue was purified via by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile/0.1% aqueous TFA over 8 minutes (10 minute run time) at a flow rate of 40 mL/minute to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 3.94 (s, 3 H) 4.55 (d, J=5.95 Hz, 2 H) 7.35-7.81 (m, 10 H) 7.99 (s, 1 H) 8.06 (d, J=8.33 Hz, 1 H) 8.37 (s, 1 H) 9.19 (t, J=5.95 Hz, 1 H) 12.98 (s, 1 H). MS (ESI(+)) m/e 426 (M+H)+.

Workup

  1. additionadded dropwise
  2. custompartitioned between brine and ethyl acetate
  3. extractionThe organic extract
  4. dry with materialwas dried with MgSO4
  5. concentrationconcentrated
  6. customthe residue was purified via by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size)
  7. customover 8 minutes
  8. custom(10 minute run time)

Sources & evidence

ORD record
ord-5b706e195c4247cb9cd7e402227c9755
Source dataset
uspto-grants-2012_10
Patent number
US08293738B2

Reaction notes

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