Diisopropylethylamine → HCID 59275609, compound

HRID 1025128Notes

Reaction equation

HRID 1025128 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:13][CH2:12][NH:11][CH2:10]2)=[CH:5][CH:4]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[O:22][C:23]3[CH:33]=[CH:32][C:31]([C:34]4[CH:35]=[C:36]([CH:40]=[CH:41][CH:42]=4)[C:37](O)=[O:38])=[CH:30][C:24]=3[C:25]=2[C:26](=[O:29])[NH:27][CH3:28])=[CH:17][CH:16]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CO>[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[O:22][C:23]3[CH:33]=[CH:32][C:31]([C:34]4[CH:42]=[CH:41][CH:40]=[C:36]([C:37]([N:11]5[CH2:12][CH2:13][CH:9]([C:6]6[CH:5]=[CH:4][C:3]([F:2])=[CH:8][CH:7]=6)[CH2:10]5)=[O:38])[CH:35]=4)=[CH:30][C:24]=3[C:25]=2[C:26]([NH:27][CH3:28])=[O:29])=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 441209833-(4-Fluorophenyl)pyrrolidine--hydrogen chloride (1/1)HCID 592754243-[2-(4-Fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-5-yl]benzoic acid

Product 1

HCID 59275609HCID 59275609, compoundYield 80.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

3-(4-Fluorophenyl)pyrrolidine hydrochloride (25 mg, 0.12 mmol) was added to a stirred suspension of 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-5-yl)benzoic acid (20 mg, 0.051 mmol), HATU (25 mg, 0.066 mmol), and DIPEA (50 μL, 0.29 mmol) in DMF (0.5 mL). The reaction was stirred at r.t. overnight, then diluted with MeOH, filtered, and purified by prep HPLC. Concentration afforded the title compound (22 mg, 79% yield) as a pink solid. 1H NMR (˜1:1 ratio of amide rotamers, 500 MHz, DMSO-d6) δ ppm 8.44-8.54 (m, 1 H) 7.98-8.06 (m, 2 H) 7.66-7.91 (m, 5 H) 7.52-7.61 (m, 2 H) 7.36-7.44 (m, 3 H) 7.33 (dd, J=8.55, 5.49 Hz, 1 H) 7.18 (t, J=8.85 Hz, 1 H) 7.12 (t, J=8.85 Hz, 1 H) 4.01 (dd, J=11.14, 7.17 Hz, 0.5 H) 3.72-3.82 (m, 1.5 H) 3.56-3.69 (m, 1.5 H) 3.36-3.55 (m, 1.5 H) 2.87 (d, J=4.58 Hz, 1.5 H) 2.84 (d, J=4.58 Hz, 1.5 H) 2.27-2.34 (m, 0.5 H) 2.24 (dd, J=6.56, 3.51 Hz, 0.5 H) 2.04-2.12 (m, 0.5 H) 2.00 (dd, J=19.84, 10.38 Hz, 0.5 H). LC/MS was performed on a Shimadzu-VP instrument with UV detection at 220 nm and Waters Micromass. LC/MS method: solvent A=10% CH3CN/90% H2O/0.1% TFA, solvent B=90% CH3CN/10% H2O/0.1% TFA, start % B=0, final % B=100, gradient time=3 min, stop time=4 min, flow rate=4 ml/min, column: Sunfire C18 5 μm 4.6×50 mm; HPLC Rt=1.89 min, (ES+) m/z (MH+)=537. Analytical HPLC method: solvent A=5% CH3CN/95% H2O/0.1% TFA, solvent B=95% CH3CN/5% H2O/0.1% TFA, start % B=10, final % B=100, gradient time=15 min, stop time=18 min, flow rate=1 ml/min. Column: Waters Sunfire C-18, 3.5 μm 4.6×150 mm, Rt=14.43 min, purity=99%; column: Waters Xbridge Phenyl 3.5 μm 4.6×150 mm, Rt=13.18 min, purity=99%.

Workup

  1. filtrationfiltered
  2. custompurified by prep HPLC
  3. concentrationConcentration

Sources & evidence

ORD record
ord-4363bd3f03584940a96bca43fa6d62fe
Source dataset
uspto-grants-2014_05
Patent number
US08722688B2

Reaction notes

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