3-Butyn-1-OL → HCID 68087380, compound

HRID 1408147Notes

Reaction equation

HRID 1408147 reaction equation
[F:1][C:2]([F:45])([F:44])[C:3]1[CH:4]=[C:5]([CH:41]=[CH:42][CH:43]=1)[CH2:6][NH:7][C:8](=[O:40])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]2[CH:20]=[C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:18]=[CH:17][C:16]=2[NH:27][C:28](=[O:39])[C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][N:36]=[N+:37]=[N-:38])[CH:30]=2)[CH:10]=1.[CH2:46]([OH:50])[CH2:47][C:48]#[CH:49]>CS(C)=O.N.O.[Cu]I>[OH:50][CH2:46][CH2:47][C:48]1[N:38]=[N:37][N:36]([CH2:35][C:31]2[CH:30]=[C:29]([CH:34]=[CH:33][CH:32]=2)[C:28]([NH:27][C:16]2[CH:17]=[CH:18][C:19]([N:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:20][C:15]=2[C:11]2[CH:10]=[C:9]([CH:14]=[CH:13][N:12]=2)[C:8]([NH:7][CH2:6][C:5]2[CH:41]=[CH:42][CH:43]=[C:3]([C:2]([F:1])([F:44])[F:45])[CH:4]=2)=[O:40])=[O:39])[CH:49]=1

Participants

6

Reactant 2

HCID 135663-Butyn-1-OLHCID 86705962HCID 86705962, compound

Product 1

HCID 68087380HCID 68087380, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 12896473Azane;hydrateSolvent

Procedure

Into a 50-mL round-bottom flask, was placed a solution of N-(3-(trifluoromethyl)benzyl)-2-(2-(3-(azidomethyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinamide (55 mg, 0.09 mmol, 1.00 equiv, 95%) in DMSO (3 mL), but-3-yn-1-ol (19 mg, 0.27 mmol, 3.00 equiv), and copper(I) iodide (0.84 mg, 0.05 equiv). The resulting solution was stirred overnight at room temperature. The resulting solution was diluted with 10 mL of 10% NH3.H2O. The resulting solution was extracted with 5×30 mL of ethyl acetate and the organic layers combined, dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude product (60 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 10 mg (14%) of a yellow to green solid. 1H-NMR (300 MHz, DMSO-d6, ppm): δ 12.48 (s, 1H), 9.55-9.58 (t, J=6 Hz, 1H), 8.93 (s, 1H), 8.36 (s, 2H), 7.96 (s, 1H), 7.85-7.96 (s, 1H), 7.71-7.77 (m, 3H) 7.64 (s, 1H), 7.55-7.60 (m, 5H), 7.44 (s, 1H), 5.67 (s, 2H), 4.63 (t, 2H), 3.58-3.61 (t, 2H), 3.40 (s, 4H), 2.75-2.77 (t, J=9 Hz, 2H), 1.61-1.78 (d, 6H). MS (ES, m/z): 684 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. extractionThe resulting solution was extracted with 5×30 mL of ethyl acetate
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum
  5. customThe crude product (60 mg) was purified by reverse phase HPLC
  6. washeluting with a water/CH3CN gradient
  7. additioncontaining 0.05% TFA
  8. customThe product was obtained as 10 mg (14%) of a yellow to green solid

Sources & evidence

ORD record
ord-64107d49718a43b3b0d13d5905f42e50
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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