Diisopropylethylamine → Ammonium Acetate

HRID 219366Notes

Reaction equation

HRID 219366 reaction equation
F[C:2](F)(F)[C:3]([O-:5])=[O:4].[CH3:8][C:9]1[N:13]=[C:12]([C:14]2([NH3+:17])[CH2:16][CH2:15]2)[O:11][N:10]=1.C(N(C(C)C)CC)(C)C.[F:27][C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([C:38]2[CH:43]=[CH:42][N:41]3[N:44]=[C:45]([C:51]4[CH:56]=[CH:55][C:54]([F:57])=[CH:53][CH:52]=4)[C:46]([C:47](=[O:50])[NH:48][CH3:49])=[C:40]3[C:39]=2[F:58])[C:36]=1[CH3:37])[C:31](O)=[O:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:3]([O-:5])(=[O:4])[CH3:2].[NH4+:10].[F:58][C:39]1[C:40]2[N:41]([N:44]=[C:45]([C:51]3[CH:52]=[CH:53][C:54]([F:57])=[CH:55][CH:56]=3)[C:46]=2[C:47]([NH:48][CH3:49])=[O:50])[CH:42]=[CH:43][C:38]=1[C:35]1[CH:34]=[C:30]([C:31](=[O:32])[NH:17][C:14]2([C:12]3[O:11][N:10]=[C:9]([CH3:8])[N:13]=3)[CH2:16][CH2:15]2)[CH:29]=[C:28]([F:27])[C:36]=1[CH3:37]

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 672172243-Fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acidHCID 866399541-(3-Methyl-1,2,4-oxadiazol-5-yl)cyclopropanaminium 2,2,2-trifluoroacetate

Product 2

HCID 517165Ammonium AcetateHCID 592337264-fluoro-5-(3-fluoro-2-methyl-5-(1-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropanaminium 2,2,2-trifluoroacetate (0.021 g, 0.083 mmol), diisopropylethylamine (0.08 mL, 0.51 mmol), 3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.028 g, 0.064 mmol) and DMF (0.43 mL) was added HATU (0.048 g, 0.13 mmol) in one portion. The solution was maintained at room temperature for 1 h and concentrated. The resultant residue was purified using preparative HPLC (Waters-Xbridge, 50×100 mm, 5 micron, C18 column; 0.1M ammonium acetate, 0-100% B (B=5% H2O/CH3CN)/A (A=95% H2O/CH3CN), 15 min. gradient) afforded 4-fluoro-5-(3-fluoro-2-methyl-5-(1-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 8.5 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.35 (d, J=7.03 Hz, 1H), 7.77-7.88 (m, 2H), 7.61 (dd, J=9.54, 1.51 Hz, 1H), 7.54 (s, 1H), 7.27-7.33 (m, 1H), 7.13-7.22 (m, 2H), 6.71 (t, J=6.65 Hz, 1H), 5.92 (d, J=4.52 Hz, 1H), 2.97 (d, J=5.02 Hz, 3H), 2.32 (s, 3H), 2.22 (s, 3H), 1.77-1.87 (m, 2H), 1.55-1.65 (m, 2H). LCMS retention time: 2.137 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 561 (MH+).

Workup

  1. concentrationconcentrated
  2. customThe resultant residue was purified

Sources & evidence

ORD record
ord-fe7e10a255c44a7986936c996f534610
Source dataset
uspto-grants-2012_06
Patent number
US08198449B2

Reaction notes

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