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-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide

HRID 2381471Notes

Reaction equation

HRID 2381471 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](O)=[O:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:28][C:29]1([CH3:41])[O:33][C@H:32]([CH2:34][N:35]2[CH:39]=[CH:38][C:37]([NH2:40])=[N:36]2)[CH2:31][O: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:40][C:37]2[CH:38]=[CH:39][N:35]([CH2:34][C@@H:32]3[CH2:31][O:30][C:29]([CH3:41])([CH3:28])[O:33]3)[N:36]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

3

Reactant 2

HCID 579193023-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid2×HCID 59344941(R)-1-((2,2-Dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine2×

Product 1

HCID 689929383-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide

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-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine (Intermediate 4) afforded 3-cyclohexyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide as a white solid as a mixture of diastereomers (2.01 g, 94%); ES+-HRMS m/e calcd for C28H33N5O5F2 [M+H+] 558.2523 found 558.2521. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.80-1.19 (m, 6H) 1.23 (s, 3H) 1.29 (s, 3H) 1.61 (br s, 5H) 1.75-1.91 (m, 1H) 2.06-2.21 (m, 1H) 3.71 (dd, J=8.5, 5.8 Hz, 1H) 3.90-4.21 (m, 3H) 4.33 (quin, J=5.8 Hz, 1H) 5.52 (dd, J=10.9, 3.9 Hz, 1H) 6.02 (d, J=2.7 Hz, 1H) 6.36 (d, J=2.1 Hz, 1H) 7.28-7.54 (m, 3H) 7.57 (d, J=2.1 Hz, 1H) 8.27 (d, J=2.7 Hz, 1H) 10.83 (s, 1H).

Sources & evidence

ORD record
ord-c4e4a9f40bee4f8eb52d635a340de429
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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