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

HRID 43998노트

반응식

HRID 43998 반응식
[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

참가 물질

9

반응물 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

생성물 2

HCID 517165Ammonium AcetateHCID 59233744HCID 59233744, 화합물

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

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+).

후처리

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

출처 및 근거

ORD 기록
ord-e466bd6c7b20427fa3012b75ce04d4b4
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08536338B2

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