Diisopropylethylamine → HCID 67482834, compound

HRID 1817773Notes

Reaction equation

HRID 1817773 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C:12]1[CH:16]=[C:15]([C:17]2[CH:26]=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[C:22]([O:27][CH3:28])[CH:23]=3)[CH:18]=2)[N:14]([C@H:29]([C:31]2[CH:39]=[CH:38][C:34]([C:35]([OH:37])=O)=[CH:33][CH:32]=2)[CH3:30])[N:13]=1.Cl.[C:41]([O:45][C:46](=[O:50])[CH2:47][CH2:48][NH2:49])([CH3:44])([CH3:43])[CH3:42].CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:10])([F:9])[F:11])=[CH:4][C:3]=1[C:12]1[CH:16]=[C:15]([C:17]2[CH:26]=[CH:25][C:24]3[C:19](=[CH:20][CH:21]=[C:22]([O:27][CH3:28])[CH:23]=3)[CH:18]=2)[N:14]([C@H:29]([C:31]2[CH:32]=[CH:33][C:34]([C:35]([NH:49][CH2:48][CH2:47][C:46]([O:45][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:50])=[O:37])=[CH:38][CH:39]=2)[CH3:30])[N:13]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 16218890Tert-butyl 3-aminopropanoate hydrochlorideHCID 67482740HCID 67482740, compound

Product 1

HCID 67482834HCID 67482834, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

4-{(1S)-1-[3-[2-Fluoro-5-(trifluoromethyl)phenyl]-5-(6-methoxy-2-naphthyl)-1H-pyrazol-1-yl]ethyl}benzoic acid (2.93 g, 5.48 mmol), beta-alanine t-butyl ester hydrochloride (2.73 g, 15 mmol), and DIEA (3.5 ml, 20 mmol) were dissolved in DMF (35 ml), followed by slow addition of PyBOP (2.93 g, 5.62 mmol) in DMF (10 ml). The reaction was stirred for 10 min, and diluted with ethyl acetate (200 ml), washed with 1N HCl 2×, 5% K2CO3 2×, and brine 2×. The solvent was evaporated and resulting residue was purified by flash chromatography (SiO2, 0-6% ethyl acetate in DCM gradient) to give tert-butyl N-(4-{(1S)-1-[3-[2-fluoro-5-(trifluoromethyl)phenyl]-5-(6-methoxy-2-naphthyl)-1H-pyrazol-1-yl]ethyl}benzoyl)-β-alaninate as a dry foam. NMR (500 MHz, DMSO-d6) δ: 1.35 (s, 9H); 1.92 (d, J=6.9 Hz, 3H); 2.44 (t, J=7.0 Hz, 2H); 3.41 (q, J=7.0 Hz, 2H); 3.89 (s, 3H); 5.80 (q, J=6.9 Hz, 1H); 6.94 (d, JF-H=3.8 Hz, 1H); 7.21 (d, J=8.3 Hz, 2H); 7.22 (dd, J=2.6 Hz, 9.0 Hz, 1H); 7.39 (d, J=2.6 Hz, 1H); 7.44 (dd, J=2.6 Hz, 8.5 Hz, 1H); 7.58 (t, J=9.7 Hz, 1H); 7.72 (d, J=8.3 Hz, 2H); 7.79 (m, 1H); 7.83 (d, J=9.0 Hz, 1H); 7.89 (d, J=2 Hz, 1H); 7.90 (d, J=8.5 Hz, 1H); 8.33 (dd, J=2.8 Hz, 6.6 Hz, 1H); 8.44 (t, J=5.5 Hz, NH). MS C37H35F4N3O4 Cald: 661.26; Obsd (M+1): 662.29.

Workup

  1. washwashed with 1N HCl 2×, 5% K2CO3 2×, and brine 2×
  2. customThe solvent was evaporated
  3. customresulting residue
  4. customwas purified by flash chromatography (SiO2, 0-6% ethyl acetate in DCM gradient)

Sources & evidence

ORD record
ord-30e61a1b60f54480a69730917afccfc4
Source dataset
uspto-grants-2009_10
Patent number
US07598285B2

Reaction notes

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