Diisopropylethylamine → Ammonium Acetate

HRID 2188983Notes

Reaction equation

HRID 2188983 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[N:4][C:3]=1[C:8]1([NH2:11])[CH2:10][CH2:9]1.C(N(C(C)C)CC)(C)C.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[C:36]([C:37](=[O:40])[NH:38][CH3:39])=[C:35]3[N:30]([N:31]=[CH:32][C:33]([C:41]4[C:42]([CH3:52])=[CH:43][C:44]([O:50][CH3:51])=[C:45]([CH:49]=4)[C:46]([OH:48])=[O:47])=[CH:34]3)[N:29]=2)=[CH:24][CH:23]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:46]([O-:48])(=[O:47])[CH3:45].[NH4+:2].[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[C:36]([C:37]([NH:38][CH3:39])=[O:40])=[C:35]3[N:30]([N:31]=[CH:32][C:33]([C:41]4[CH:49]=[C:45]([C:46](=[O:47])[NH:11][C:8]5([C:3]6[N:4]=[CH:5][CH:6]=[CH:7][N:2]=6)[CH2:10][CH2:9]5)[C:44]([O:50][CH3:51])=[CH:43][C:42]=4[CH3:52])=[CH:34]3)[N:29]=2)=[CH:24][CH:23]=1

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 569656581-(Pyrimidin-2-yl)cyclopropan-1-amine hydrochlorideHCID 66763514HCID 66763514, compound

Product 2

HCID 517165Ammonium AcetateHCID 53378805HCID 53378805, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution containing 1-(pyrimidin-2-yl)cyclopropanamine hydrochloride (0.008 g, 0.05 mmol), diisopropylethylamine (0.05 mL, 0.28 mmol), 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-b]pyridazin-5-yl)-2-methoxy-4-methylbenzoic acid (0.015 g, 0.04 mmol) and DMF (0.23 mL) was added HATU (0.026 g, 0.07 mmol) in one portion. The solution was maintained at room temperature for 1 h. The product 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) to afford 2-(4-fluorophenyl)-5-(4-methoxy-2-methyl-5-(1-(pyrimidin-2-yl)cyclopropylcarbamoyl)phenyl)-N-methylpyrazolo[1,5-b]pyridazine-3-carboxamide as a white solid. Preparative HPLC retention time: 10.5 min. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.72-8.58 (m, 4H), 8.41 (d, J=2.3 Hz, 1H), 8.23 (s, 1H), 7.83-7.74 (m, 2H), 7.26-7.20 (m, 1H), 7.10-7.03 (m, 1H), 6.98 (s, 1H), 5.66 (br. s., 1H), 4.09 (s, 3H), 2.88 (d, J=4.8 Hz, 3H), 2.46 (s, 3H), 1.88-1.81 (m, 2H), 1.59-1.52 (m, 2H). LCMS retention time: 2.057 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 3 micron, C18, 2.0×50 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 1.0 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% methanol/90% H2O/10 mM TFA and solvent B was 10% H2O/90% methanol/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 552 (MH+).

Workup

  1. customThe product was purified

Sources & evidence

ORD record
ord-51f7e2d0f26a4345bffeded9151cd63d
Source dataset
uspto-grants-2012_12
Patent number
US08324212B2

Reaction notes

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