Diisopropylethylamine → HCID 67482670, compound

HRID 1715512Notes

Reaction equation

HRID 1715512 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:24][CH3:25])[CH:20]=4)[CH:15]=3)[N:11]([C@H:26]([C:28]3[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=3)[CH3:27])[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl.[C:38]([O:42][C:43](=[O:47])[CH2:44][CH2:45][NH2:46])([CH3:41])([CH3:40])[CH3:39].CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([C:14]3[CH:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[C:19]([O:24][CH3:25])[CH:20]=4)[CH:15]=3)[N:11]([C@H:26]([C:28]3[CH:29]=[CH:30][C:31]([C:32]([NH:46][CH2:45][CH2:44][C:43]([O:42][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:47])=[O:33])=[CH:35][CH:36]=3)[CH3:27])[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 16218890Tert-butyl 3-aminopropanoate hydrochlorideHCID 57882754HCID 57882754, compound

Product 1

HCID 67482670HCID 67482670, compound

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-{(1S)-1-[3-(3,5-Dichlorophenyl)-5-(6-methoxy-2-naphthyl)-1H-pyrazol-1-yl]ethyl}benzoic acid (3.5 g, 6.76 mmol), beta-alanine t-butyl ester hydrochloride (3.7 g, 20 mmol), DIEA (3.53 ml, 20 mmol), and DMAP (40 mg, 5%) were dissolved in DCM (50 ml), followed by addition of solid EDC HCl (1.6 g, 8.1 mmol). More EDC HCl (1.8 g) was added after one hour. The reaction was completed in about 3 hr as monitored by LC-MS. Ethyl acetate was added to the reaction mixture, and this was washed with 1N HCl 3× and brine 2×. The crude product was then purified by column chromatography (SiO2, 0-6% ethyl acetate in DCM) to give tert-butyl N-(4-{(1S)-1-[3-(3,5-dichlorophenyl)-5-(6-methoxy-2-naphthyl)-1H-pyrazol-1-yl]ethyl}benzoyl)-β-alaninate as a dry foam. NMR (500 MHz, DMSO-d6) δ: 1.36 (s, 9H); 1.90 (d, J=6.9 Hz, 3H); 2.44 (t, J=6.8 Hz, 2H); 3.41 (q, J=6.8 Hz, 2H); 3.89 (s, 3H); 5.76 (q, J=6.9 Hz, 1H); 7.15 (s, 1H); 7.21 (d, J=8.4 Hz, 2H); 7.22 (dd, J=2.6, 9.0 Hz, 1H); 7.38 (d, J=2.6 Hz, 1H); 7.43 (dd, J=1.9, 8.5 Hz, 1H); 7.55 (t, J=1.9 Hz, 1H); 7.71 (d, J=8.4 Hz, 2H); 7.81 (d, J=9.0 Hz, H); 7.85 (d, J=1.9 Hz, 1H); 7.90 (d, J=8.5 Hz, 1H); 7.92 (d, J=1.9 Hz, 2H); 8.44 (t, J=5.2 Hz, 1H).

Workup

  1. washthis was washed with 1N HCl 3× and brine 2×
  2. customThe crude product was then purified by column chromatography (SiO2, 0-6% ethyl acetate in DCM)

Sources & evidence

ORD record
ord-1ca36eced9e040619fc09e8ae3818570
Source dataset
uspto-grants-2010_09
Patent number
US07799818B2

Reaction notes

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