Diisopropylethylamine → Tert-butyl 7-fluoro-2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate

HRID 44050Notes

Reaction equation

HRID 44050 reaction equation
Cl.[C:2]1([C:8]2([NH2:11])[CH2:10][CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.[C:21]([O:25][C:26]([N:28]([CH3:58])[C:29]([C:31]1[C:32]([C:51]2[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=2)=[N:33][N:34]2[C:39]([F:40])=[CH:38][C:37]([C:41]3[CH:42]=[C:43]([CH:47]=[CH:48][C:49]=3[CH3:50])[C:44](O)=[O:45])=[CH:36][C:35]=12)=[O:30])=[O:27])([CH3:24])([CH3:23])[CH3:22].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:40][C:39]1[N:34]2[N:33]=[C:32]([C:51]3[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=3)[C:31]([C:29]([N:28]([CH3:58])[C:26](=[O:27])[O:25][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:30])=[C:35]2[CH:36]=[C:37]([C:41]2[CH:42]=[C:43]([C:44](=[O:45])[NH:11][C:8]3([C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH2:10][CH2:9]3)[CH:47]=[CH:48][C:49]=2[CH3:50])[CH:38]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1945481-PhenylcyclopropylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592338333-(3-(Tert-butoxycarbonyl(methyl)carbamoyl)-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

Product 1

HCID 59233824Tert-butyl 7-fluoro-2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-phenylcyclopropanamine hydrochloride (0.010 g, 0.061 mmol), diisopropylethylamine (0.086 mL, 0.49 mmol), 3-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.032 g, 0.061 mmol) and DMF (0.41 mL) was added HATU (0.047 g, 0.12 mmol) in one portion. The solution was maintained at room temperature for 1 h and concentrated. The resultant residue was purified on silica gel (30-100% ethyl acetate/hexanes, 45 min. gradient) to afford tert-butyl 7-fluoro-2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate as a residue. LCMS retention time: 2.938 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, 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 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% CH3OH/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3OH/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 637 (MH+).

Workup

  1. concentrationconcentrated
  2. customThe resultant residue was purified on silica gel (30-100% ethyl acetate/hexanes, 45 min. gradient)

Sources & evidence

ORD record
ord-9c7ada86bfce46798cc5443023db5fa2
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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