N,N,N',N'-Tetramethylazodicarboxamide → 6-{2-[2-(4-Chloro-2-methyl-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethoxy}-nicotinic acid methyl ester

HRID 417132Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:14][OH:15])[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=2)=[C:4]([CH3:28])[CH:3]=1.O[C:30]1[CH:39]=[CH:38][C:33]([C:34]([O:36][CH3:37])=[O:35])=[CH:32][N:31]=1.C(P(CCCC)CCCC)CCC.CN(C)C(N=NC(N(C)C)=O)=O>O1CCCC1>[CH3:37][O:36][C:34](=[O:35])[C:33]1[CH:38]=[CH:39][C:30]([O:15][CH2:14][CH:13]([N:12]2[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=[C:8]2[C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[CH3:28])[CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)=[N:31][CH:32]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 200 mg (0.494 mmol) 2-[2-(4-chloro-2-methyl-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol in 5 ml tetrahydrofuran were added 83 mg (0.543 mmol) methyl 6-hydroxynicotinate (commercially available) and 120 mg (0.593 mmol) tri-n-butylphosphin. The reaction mixture was cooled down to 0° C. 102 mg (0.593 mmol) N,N,N′,N′-tetramethylazodicarboxamide were added. The reaction mixture was stirred for 18 hours at room temperature and then concentrated under vacuum. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 70:30). Light yellow solid (29%). MS (Turbo Spray): m/z=540.2 [M+H].

Workup

concentrationconcentrated under vacuum
customThe residue was purified by silica gel chromatography
washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 70:30)

Sources & evidence

ORD record: ord-87b1b255fe1247c890a05b0a2f5c7100
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088930B2

Reaction notes

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