5-Methoxythiazole-2-carboxylic acid → (R)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-methoxythiazole-2-carboxamide

HRID 872540Notes

Reaction equation

HRID 872540 reaction equation
[NH2:1][C@H:2]([CH3:18])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([Cl:17])[CH:10]=2)=[N:5]1.[CH3:19][O:20][C:21]1[S:25][C:24]([C:26](O)=[O:27])=[N:23][CH:22]=1>>[Cl:17][C:11]1[CH:10]=[C:9]([C:6]2[CH:7]=[CH:8][N:4]([CH2:3][C@H:2]([NH:1][C:26]([C:24]3[S:25][C:21]([O:20][CH3:19])=[CH:22][N:23]=3)=[O:27])[CH3:18])[N:5]=2)[CH:16]=[CH:15][C:12]=1[C:13]#[N:14]

Participants

3

Reactant 2

HCID 671700935-Methoxythiazole-2-carboxylic acidHCID 67171309(R)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile

Product 1

HCID 70656695(R)-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-5-methoxythiazole-2-carboxamideYield 9%

Procedure

(R)-4-(1-(2-aminopropyl)-1H-pyrazol-3-yl)-2-chlorobenzonitrile (86 mg, 0.33 mmol) was coupled with 5-methoxythiazole-2-carboxylic acid (90 mg, 0.40 mmol) using the method of Example 34(d). Crude product was purified by CombiFlash (column: silica, eluent: 0-10% MeOH in DCM) to yield 12 mg (9%) of the title compound. 1H-NMR (400 MHz; CDCl3): δ 1.23 (d, 3H), 3.99 (s, 3H), 4.26 (dd, 1H), 4.40-4.46 (m, 1H), 4.49-4.59 (m, 1H), 6.63 (d, 1H), 7.22 (s, 1H), 7.49 (d, 1H), 7.68 (d, 1H), 7.78 (dd, 1H), 8.10 (broad d, 1H) overlapping with 8.13 (d, 1H).

Workup

  1. customCrude product was purified by CombiFlash (column: silica, eluent: 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-d1e805de8f894ea08ab8bd692f3f0152
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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