2-Chloro-3-methoxyphenol → 2-[4-(2-chloro-3-methoxy-phenoxy)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

HRID 2381550Notes

Reaction equation

HRID 2381550 reaction equation
[CH3:1][C:2]1([CH3:29])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:28])[CH:15]([N:20]3[C:25](=[O:26])[CH:24]=[C:23](I)[CH:22]=[N:21]3)[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1.[Cl:30][C:31]1[C:36]([O:37][CH3:38])=[CH:35][CH:34]=[CH:33][C:32]=1[OH:39]>>[CH3:1][C:2]1([CH3:29])[O:6][C@H:5]([CH2:7][N:8]2[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:28])[CH:15]([N:20]3[C:25](=[O:26])[CH:24]=[C:23]([O:39][C:32]4[CH:33]=[CH:34][CH:35]=[C:36]([O:37][CH3:38])[C:31]=4[Cl:30])[CH:22]=[N:21]3)[CH2:16][CH:17]([CH3:19])[CH3:18])=[N:9]2)[CH2:4][O:3]1

Participants

3

Reactant 2

HCID 155814712-Chloro-3-methoxyphenolHCID 579192872-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide2×

Product 1

HCID 668933082-[4-(2-chloro-3-methoxy-phenoxy)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide

Procedure

Using the method described in Example 126, Step 1,2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (Intermediate 94) and 2-chloro-3-methoxy-phenol afforded 2-[4-(2-chloro-3-methoxy-phenoxy)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide as a white solid as a mixture of diastereomers (42 mg, 77%); ES+-HRMS m/e calcd for C26H32N5O6Cl [M+H+] 546.2114 found 546.2114. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.78-0.97 (m, 6H), 1.24 (s, 3H), 1.30 (2×s, 3H), 1.45 (br. s., 1H), 1.69-1.87 (m, 1H), 2.05-2.25 (m, 1H), 3.73 (dd, J=8.5, 5.7 Hz, 1H), 3.92 (s, 3H), 4.00 (dd, J=8.5, 6.3 Hz, 1H), 4.04-4.19 (m, 2H), 4.35 (quin, J=5.8 Hz, 1H), 5.51 (dd, J=11.0, 4.1 Hz, 1H), 5.71 (d, J=2.7 Hz, 1H), 6.38 (d, J=2.4 Hz, 1H), 7.06 (d, J=8.2 Hz, 1H), 7.18 (d, J=8.2 Hz, 1H), 7.45 (t, J=8.2 Hz, 1H), 7.59 (s, 1H), 8.19 (d, J=2.7 Hz, 1H), 10.84 (s, 1H).

Sources & evidence

ORD record
ord-e0ad841eb89f4d6bb2c293690952602d
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

Loading…