1H-imidazole-2-carbaldehyde → di-tert-butyl 4-(3-(tert-butoxy)-3-oxopropyl)-4-(2-(2-formyl-1H-imidazol-1-yl)acetamido)heptanedioate

HRID 2273339Notes

Reaction equation

HRID 2273339 reaction equation
Br[CH2:2][C:3]([NH:5][C:6]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])([CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:7][CH2:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:4].[NH:34]1[CH:38]=[CH:37][N:36]=[C:35]1[CH:39]=[O:40].CCN(C(C)C)C(C)C>CN(C=O)C>[C:12]([O:11][C:9](=[O:10])[CH2:8][CH2:7][C:6]([NH:5][C:3](=[O:4])[CH2:2][N:34]1[CH:38]=[CH:37][N:36]=[C:35]1[CH:39]=[O:40])([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:16][CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])([CH3:15])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 249551H-imidazole-2-carbaldehydeHCID 81531DiisopropylethylamineHCID 24728093Di-tert-butyl 4-(2-bromoacetamido)-4-(3-(tert-butoxy)-3-oxopropyl)heptanedioate

Product 1

HCID 86692716di-tert-butyl 4-(3-(tert-butoxy)-3-oxopropyl)-4-(2-(2-formyl-1H-imidazol-1-yl)acetamido)heptanedioateYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of di-tert-butyl 4-(2-bromoacetamido)-4-(3-(tert-butoxy)-3-oxopropyl)heptanedioate (1.397 g, 2.61 mmol), 1H-imidazole-2-carbaldehyde (0.30 g, 3.13 mmol), DIPEA (2.0 mL), and KI (0.30 g) in DMF (5.0 mL) was stirred at 80° C. for 5 hrs. The solvent was evaporated under reduced pressure to afford a residue, which was purified by biotage eluting with 20% EtOAc in hexanes to 100% EtOAc to give di-tert-butyl 4-(3-(tert-butoxy)-3-oxopropyl)-4-(2-(2-formyl-1H-imidazol-1-yl)acetamido)heptanedioate (0.90 g, 63%). 1H NMR (400 MHz, CDCl3) 9.78 (s, 1H), 7.32 (s, 1H), 7.23 (s, 1H), 6.65 (s, 1H), 4.90 (s, 2H), 2.19 (t, J=7.8 Hz, 6H), 1.94 (t, J=7.8 Hz, 6H), 1.42 (s, 9H); MS (ESI), 552 (M+H)+.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customto afford a residue, which
  3. customwas purified by biotage
  4. washeluting with 20% EtOAc in hexanes to 100% EtOAc

Sources & evidence

ORD record
ord-86bb5f95c41245ec94d25ddc53232261
Source dataset
uspto-grants-2015_09
Patent number
US09120837B2

Reaction notes

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