Tert-Butylamine → HCID 59233666, compound

HRID 44083Notes

Reaction equation

HRID 44083 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:34][C:20]3=[N:21][CH:22]=[C:23]([C:25]4[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=4)[C:28]([OH:30])=O)[CH:24]=[C:19]3[C:18]=2[C:35](=[O:38])[NH:36][CH3:37])=[CH:13][CH:12]=1.[CH3:39][C:40]([NH2:43])([CH3:42])[CH3:41].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CCOC(C)=O>[C:40]([NH:43][C:28]([C:27]1[CH:26]=[C:25]([C:23]2[CH:24]=[C:19]3[C:18]([C:35]([NH:36][CH3:37])=[O:38])=[C:17]([C:14]4[CH:15]=[CH:16][C:11]([F:10])=[CH:12][CH:13]=4)[O:34][C:20]3=[N:21][CH:22]=2)[CH:33]=[CH:32][CH:31]=1)=[O:30])([CH3:42])([CH3:41])[CH3:39]

Participants

7

Reactant 4

HCID 6385Tert-ButylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672176353-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoic acid

Product 1

HCID 59233666HCID 59233666, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIEA (31 μL, 0.18 mmol) was added to a stirring solution of 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)benzoic acid (23 mg, 0.059 mmol), 2-methylpropan-2-amine (20 μL, 0.059 mmol), and HATU (27 mg, 0.071 mmol) in DMF (0.6 mL) at room temperature. It was allowed to stir for 2 hours. The mixture was diluted with EtOAc and washed with 1M HCl, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated to give the expected product 5-(3-(tert-butylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylfuro[2,3-b]pyridine-3-carboxamide (8 mg, 0.017 mmol, 29% yield) consistent by LCMS and NMR. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.74 (1H, d, J=2.14 Hz), 8.55-8.61 (1H, m), 8.39 (1H, d, J=2.44 Hz), 8.16 (1H, s), 8.07 (2H, dd, J=8.85, 5.19 Hz), 7.94 (1H, s), 7.92 (1H, d, J=7.63 Hz), 7.86 (1H, d, J=7.93 Hz), 7.59 (1H, t, J=7.63 Hz), 7.43 (2 H, t, J=8.85 Hz), 2.87 (3H, d, J=4.58 Hz), 1.42 (9H, s). LC-MS retention time: 1.68 min; m/z (MH+): 446. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 10u C18 3.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. Additional HPLC method: Solvent A=5% MeOH/95% H2O/10 mM ammonium bicarbonate, Solvent B=95% MeOH/5% H2O/10 mM ammonium bicarbonate, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column. Phenomenex Gemini C1 C-18, 4.6×150 mm, 3 mm, Rt=13.66 min, purity=98%; Column: Waters Xbridge Phenyl column 4.6×150 mm, 3.5 mm, Rt=13.69 min, purity=98%.

Workup

  1. washwashed with 1M HCl
  2. dry with materialThe organic phase was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-7ed3af629db34464aa621298b43fd322
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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