Diisopropylethylamine → Ammonium Acetate

HRID 44044Notes

Reaction equation

HRID 44044 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.[F:21][C:22]1[CH:23]=[C:24]([CH:28]=[C:29]([C:32]2[CH:37]=[CH:36][N:35]3[N:38]=[C:39]([C:45]4[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=4)[C:40]([C:41](=[O:44])[NH:42][CH3:43])=[C:34]3[C:33]=2[F:52])[C:30]=1[CH3:31])[C:25]([OH:27])=[O:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:25]([O-:27])(=[O:26])[CH3:24].[NH4+:11].[F:52][C:33]1[C:34]2[N:35]([N:38]=[C:39]([C:45]3[CH:46]=[CH:47][C:48]([F:51])=[CH:49][CH:50]=3)[C:40]=2[C:41]([NH:42][CH3:43])=[O:44])[CH:36]=[CH:37][C:32]=1[C:29]1[CH:28]=[C:24]([C:25](=[O:26])[NH:11][C:8]2([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:10][CH2:9]2)[CH:23]=[C:22]([F:21])[C:30]=1[CH3:31]

Participants

7

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 672172243-Fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid

Product 2

HCID 517165Ammonium AcetateHCID 592337514-fluoro-5-(3-fluoro-2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-phenylcyclopropanamine hydrochloride (0.059 g, 0.027 mmol), diisopropylethylamine (0.04 mL, 0.22 mmol), 3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.012 g, 0.027 mmol) and DMF (0.19 mL) was added HATU (0.021 g, 0.055 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), 20 min. gradient) afforded 4-fluoro-5-(3-fluoro-2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 15.0 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.36 (d, J=7.03 Hz, 1H), 7.80-7.89 (m, 2H), 7.56 (d, J=9.79 Hz, 1H), 7.51 (s, 1H), 7.28-7.36 (m, 4H), 7.13-7.25 (m, 3H), 6.91 (s, 1H), 6.72 (t, J=6.78 Hz, 1H), 5.85 (d, J=4.27 Hz, 1H), 2.97 (d, J=4.77 Hz, 3H), 2.23 (s, 3H), 1.38 (s, 4 H). LCMS retention time: 2.437 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 555 (MH+).

Workup

  1. concentrationconcentrated
  2. customThe resultant residue was purified

Sources & evidence

ORD record
ord-1616467a20cb4870a5b595f42c502579
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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