3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid → 3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide

HRID 2381457Notes

Reaction equation

HRID 2381457 reaction equation
[CH:1]1([CH2:7][CH:8]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([O:19][C:20]3[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=3[F:27])[CH:14]=[N:13]2)[C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:28][C:29]1[CH:33]=[CH:32][N:31]([CH2:34][C:35]([CH3:38])([OH:37])[CH3:36])[N:30]=1>>[CH:1]1([CH2:7][CH:8]([N:12]2[C:17](=[O:18])[CH:16]=[C:15]([O:19][C:20]3[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=3[F:27])[CH:14]=[N:13]2)[C:9]([NH:28][C:29]2[CH:33]=[CH:32][N:31]([CH2:34][C:35]([OH:37])([CH3:36])[CH3:38])[N:30]=2)=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

3

Reactant 2

HCID 579193023-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid2×HCID 593449381-(3-amino-1H-pyrazol-1-yl)-2-methylpropan-2-ol2×

Product 1

HCID 444663543-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamideYield 98%

Procedure

Using the method described in Example 49, 3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (Intermediate 33) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (Intermediate 1) afforded 3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-propionamide as a white solid (2.0 g, 98%); ES+-HRMS m/e calcd for C26H31N5O4F2 [M+H+] 516.2417 found 516.2417. 1H-NMR (300 MHz, DMSO-d6) δ ppm 0.78-1.26 (m, 6H) 1.03 (s, 3H) 1.04 (s, 3H) 1.45-1.70 (m, 5H) 1.73-1.91 (m, 1H) 2.01-2.24 (m, 1H) 3.87 (s, 2H) 4.66 (s, 1H) 5.52 (dd, J=11.0, 4.1 Hz, 1H) 6.02 (d, J=2.7 Hz, 1H) 6.37 (d, J=2.2 Hz, 1H) 7.24-7.49 (m, 3H) 7.51 (d, J=2.2 Hz, 1H) 8.27 (d, J=2.7 Hz, 1H) 10.83 (s, 1H).

Sources & evidence

ORD record
ord-460de4ccd07d4050a389b016aac2899e
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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