Cumylamine → Ammonium Acetate

HRID 44001Notes

Reaction equation

HRID 44001 reaction equation
[C:1]1([C:7]([NH2:10])([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(C(C)C)CC)(C)C.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:44]([C:45](=[O:48])[NH:46][CH3:47])=[C:30]3[CH:31]=[C:32]([C:35]4[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=4)[C:38]([OH:40])=[O:39])[CH:33]=[CH:34][N:29]3[N:28]=2)=[CH:23][CH:22]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:38]([O-:40])(=[O:39])[CH3:37].[NH4+:10].[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:44]([C:45]([NH:46][CH3:47])=[O:48])=[C:30]3[CH:31]=[C:32]([C:35]4[CH:43]=[CH:42][CH:41]=[C:37]([C:38](=[O:39])[NH:10][C:7]([C:1]5[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=5)([CH3:9])[CH3:8])[CH:36]=4)[CH:33]=[CH:34][N:29]3[N:28]=2)=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 68509CumylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 592336733-(2-(4-Fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)benzoic acid

Product 2

HCID 517165Ammonium AcetateHCID 592337722-(4-fluorophenyl)-N-methyl-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 2-phenylpropan-2-amine (0.040 g, 0.29 mmol), diisopropylethylamine (0.10 mL, 0.58 mmol), 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)benzoic acid (0.10 g, 0.20 mmol) and DMF (1.3 mL) was added HATU (0.10 g, 0.25 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), 12 min. gradient) afforded 2-(4-fluorophenyl)-N-methyl-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC: retention time: 8.0 min. 1H NMR (500 MHz, DMSO-D6) δ ppm 8.90 (d, J=7.32 Hz, 1H), 8.65 (s, 1H), 8.26 (s, 1H), 8.10 (s, 1H), 8.00 (d, J=6.10 Hz, 2H), 7.88-7.94 (m, 3H), 7.61-7.66 (m, 1H), 7.49 (dd, J=7.17, 1.68 Hz, 1H), 7.42 (d, J=7.63 Hz, 2H), 7.28-7.35 (m, 4 H), 7.19 (s, 1H), 2.81 (d, J=4.58 Hz, 3H), 1.72 (s, 6H). LCMS: retention time: 3.325 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10u, C18, 4.6×50 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 507 (MH+).

Workup

  1. concentrationconcentrated
  2. customThe resultant residue was purified

Sources & evidence

ORD record
ord-e97711b7edd24ab5bec657ea826ab233
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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