(S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine → 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide

HRID 2381473Notes

Reaction equation

HRID 2381473 reaction equation
[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[CH:13]=[N:12]2)[C:8](O)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:27][C:28]1([CH3:40])[O:32][C@@H:31]([CH2:33][N:34]2[CH:38]=[CH:37][C:36]([NH2:39])=[N:35]2)[CH2:30][O:29]1>>[CH:1]1([CH2:6][CH:7]([N:11]2[C:16](=[O:17])[CH:15]=[C:14]([O:18][C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[CH:13]=[N:12]2)[C:8]([NH:39][C:36]2[CH:37]=[CH:38][N:34]([CH2:33][C@H:31]3[CH2:30][O:29][C:28]([CH3:40])([CH3:27])[O:32]3)[N:35]=2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

3

Reactant 2

HCID 57346939(S)-1-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-1H-pyrazol-3-amine2×HCID 579193033-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid2×

Product 1

HCID 668936033-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide

Procedure

Using the method described in Example 17, 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-propionic acid (Intermediate 47) and 1-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-ylamine (Intermediate 5) afforded 3-cyclopentyl-2-[4-(2,6-difluoro-phenoxy)-6-oxo-6H-pyridazin-1-yl]-N-[1-((S)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-propionamide as a white solid as a mixture of diastereomers (142.6 mg, 38%). 1H NMR (300 MHz, DMSO-d6) δ ppm 1.17 (m, 2H), 1.25 (s, 3H), 1.30 (s, 3H), 1.35-1.77 (m, 7H), 1.86-2.02 (m, 1H), 2.20-2.33 (m, 1H), 3.73 (dd, J=8.3, 5.9 Hz, 1H), 3.97-4.17 (m, 3H), 4.30-4.41 (m, 1H), 5.46 (dd, J=10.6, 4.2 Hz, 1H), 6.03 (d, J=2.6 Hz, 1H), 6.39 (d, J=2.1 Hz, 1H), 7.31-7.55 (m, 3H), 7.59 (br s, 1H), 8.22-8.33 (m, 1H), 10.73-10.94 (m, 1H).

Sources & evidence

ORD record
ord-9c00fb661f36461da637a1f1e0df2dac
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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