1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → Ammonium Acetate

HRID 43998Notes

Reaction equation

HRID 43998 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:42]([C:43]([OH:45])=[O:44])=[C:11]3[CH:12]=[C:13]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30](=[O:41])[NH:31][C:32]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)([CH3:34])[CH3:33])[CH:25]=4)[C:14]([N:16]([CH2:21][CH2:22][OH:23])[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1.C1C=[N:50][C:49]2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.CN.CCN=C=NCCCN(C)C>CN(C=O)C.ClCCl>[C:43]([O-:45])(=[O:44])[CH3:42].[NH4+:9].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:42]([C:43]([NH:50][CH3:49])=[O:45])=[C:11]3[CH:12]=[C:13]([C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([C:30](=[O:41])[NH:31][C:32]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)([CH3:33])[CH3:34])[CH:25]=4)[C:14]([N:16]([CH2:21][CH2:22][OH:23])[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:15][N:10]3[N:9]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 6364545Methylamine hydrochlorideHCID 592336792-(4-fluorophenyl)-6-(N-(2-hydroxyethyl)methylsulfonamido)-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxylic acid

Product 2

HCID 517165Ammonium AcetateHCID 59233744HCID 59233744, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution containing 2-(4-fluorophenyl)-6-(N-(2-hydroxyethyl)methylsulfonamido)-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxylic acid (0.021 g, 0.033 mmol), HOAT (0.0050 g, 0.036 mmol), diisopropylethylamine (0.070 mL, 0.40 mmol), methylamine hydrochloride (0.0090 g, 0.13 mmol), dichloromethane (0.70 mL) and DMF (0.14 mL) was added EDCI (0.020 g, 0.10 mmol). The solution was maintained at room temperature for 15 h and concentrated. Purification by 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)-6-(N-(2-hydroxyethyl)methylsulfonamido)-N-methyl-5-(3-(2-phenylpropan-2-ylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time 7.4 min. 1H NMR (400 MHz, DMSO-D6) δ ppm 9.13 (s, 1H), 8.28 (s, 1H), 8.05 (s, 1H), 8.00 (q, J=4.27 Hz, 1H), 7.86-7.94 (m, 3 H), 7.78 (d, J=8.03 Hz, 1H), 7.75 (s, 1H), 7.56 (t, J=7.78 Hz, 1H), 7.37-7.42 (m, 2 H), 7.25-7.35 (m, 4H), 7.16 (t, J=7.28 Hz, 1H), 4.95 (t, J=4.89 Hz, 1H), 3.58 (dd, J=14.18, 5.65 Hz, 1H), 3.38 (s, 2H), 3.21-3.26 (m, 3H), 2.86-2.96 (m, 1H), 2.75 (d, J=4.52 Hz, 3H), 1.67 (s, 6H). LCMS: retention time: 2.825 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10u, 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 4 min, a hold time of 1 min, and an analysis time of 5 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 644 (MH+).

Workup

  1. concentrationconcentrated
  2. customPurification by preparative HPLC (Waters—Xbridge, 50×100 mm, 5 micron, C18 column

Sources & evidence

ORD record
ord-e466bd6c7b20427fa3012b75ce04d4b4
Source dataset
uspto-grants-2013_09
Patent number
US08536338B2

Reaction notes

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