Dimethylformamide → tert-butyl 1-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-1-oxopropan-2-ylcarbamate

HRID 883102Notes

Reaction equation

HRID 883102 reaction equation
[N:1]([CH2:4][CH2:5][CH2:6][C:7]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[NH:11][N:10]=[C:9]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[F:19])[S:8]1)=[N+:2]=[N-:3].[C:26]([O:30][C:31](C(C)C(O)=O)=[O:32])([CH3:29])([CH3:28])[CH3:27].CCN=C=NC[CH2:44][CH2:45][N:46](C)C.C1C=CC2N(O)N=NC=2C=1.CN([CH:62]=[O:63])C>>[N:1]([CH2:4][CH2:5][CH2:6][C:7]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:11]([C:62](=[O:63])[CH:45]([NH:46][C:31](=[O:32])[O:30][C:26]([CH3:27])([CH3:28])[CH3:29])[CH3:44])[N:10]=[C:9]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=2[F:19])[S:8]1)=[N+:2]=[N-:3]

Participants

6

Reactant 5

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 178517023-(Tert-butoxy)-2-methyl-3-oxopropanoic acidHCID 866048312-(3-Azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazole

Product 1

HCID 86604830tert-butyl 1-(2-(3-azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-1,3,4-thiadiazol-3(2H)-yl)-1-oxopropan-2-ylcarbamateYield 94%

Conditions

Temperature
23 °C

Procedure

2-(3-Azidopropyl)-5-(2,5-difluorophenyl)-2-phenyl-2,3-dihydro-1,3,4-thiadiazole (50 mg, 0.139 mmol; as prepared in example 70) was dissolved in 2.0 mL of DMF. 2-(tert-Butoxycarbonyl)propanoic acid (39 mg, 0.208 mmol), EDCI (40 mg, 0.208 mmol), HOBt (28 mg, 0.208 mmol) and TEA (0.058 mL, 0.417 mmol) were then added and the reaction allowed to stir at 23° C. Following 12 hours, the reaction was quenched by addition of saturated NaHCO3 solution, extracted (3×15 mL ethyl acetate), combined organics washed with water (1×50 mL) then dried over Na2SO4, and concentrated in vacuo. The crude reaction was purified by chromatography (20% ethyl acetate/Hex) affording the product as a white foam (70 mg, 94%). MS APCI (−) m/z 529 (M−1) detected; 1H NMR (400 MHz, CDCl3) δ 7.59 (m, 1H), 7.43 (m, 2H), 7.37 (t, 2H, J=8 Hz), 7.30 (m, 1H), 7.12 (m, 2H), 5.23 (brs, 0.5H), 5.12 (brs, 0.5H), 3.44 (m, 2H), 3.19 (m, 1H), 2.47 (m, 1H), 1.57 (d, 2H, J=9 Hz), 1.43 (m, 12H), 0.89 (m, 1H).

Workup

  1. customthe reaction was quenched by addition of saturated NaHCO3 solution
  2. extractionextracted (3×15 mL ethyl acetate)
  3. washcombined organics washed with water (1×50 mL)
  4. dry with materialthen dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude reaction
  7. customwas purified by chromatography (20% ethyl acetate/Hex)

Sources & evidence

ORD record
ord-497a8b7358c747ae86e42aab22d13111
Source dataset
uspto-grants-2012_08
Patent number
US08236825B2

Reaction notes

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