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

HRID 44051Notes

Reaction equation

HRID 44051 reaction equation
Cl.Cl.[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1([NH2:12])[CH2:11][CH2:10]1.C(N(C(C)C)CC)(C)C.[C:22]([O:26][C:27]([N:29]([CH3:59])[C:30]([C:32]1[C:33]([C:52]2[CH:57]=[CH:56][C:55]([F:58])=[CH:54][CH:53]=2)=[N:34][N:35]2[C:40]([F:41])=[CH:39][C:38]([C:42]3[CH:43]=[C:44]([CH:48]=[CH:49][C:50]=3[CH3:51])[C:45](O)=[O:46])=[CH:37][C:36]=12)=[O:31])=[O:28])([CH3:25])([CH3:24])[CH3:23].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[F:41][C:40]1[N:35]2[N:34]=[C:33]([C:52]3[CH:57]=[CH:56][C:55]([F:58])=[CH:54][CH:53]=3)[C:32]([C:30]([N:29]([CH3:59])[C:27](=[O:28])[O:26][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:31])=[C:36]2[CH:37]=[C:38]([C:42]2[CH:43]=[C:44]([C:45](=[O:46])[NH:12][C:9]3([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][N:3]=4)[CH2:11][CH2:10]3)[CH:48]=[CH:49][C:50]=2[CH3:51])[CH:39]=1

Participants

6

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 533931811-(2-Pyridyl)cyclopropylamine DihydrochlorideHCID 592338333-(3-(Tert-butoxycarbonyl(methyl)carbamoyl)-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

Product 1

HCID 59233755Tert-butyl 7-fluoro-2-(4-fluorophenyl)-5-(2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-(pyridin-2-yl)cyclopropanamine dihydrochloride (0.011 g, 0.054 mmol), diisopropylethylamine (0.075 mL, 0.43 mmol), 3-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-7-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.028 g, 0.054 mmol) and DMF (0.36 mL) was added HATU (0.041 g, 0.11 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-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carbonyl(methyl)carbamate as a residue. LCMS retention time: 2.428 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 638 (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-e1da070e572344f58c20afe514b7aa37
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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