Dicyclohexylcarbodiimide → HCID 10277134, compound

HRID 1698899Notes

Reaction equation

HRID 1698899 reaction equation
[NH2:1][CH2:2][C:3]1[S:4][C:5]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:6][C:7]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=1)=[O:10].[C:23]([NH:30][CH2:31][C:32](O)=[O:33])([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].C1(N=C=NC2CCCCC2)CCCCC1.O.ON1C2C=CC=CC=2N=N1>C1COCC1.CCOC(C)=O>[C:23]([NH:30][CH2:31][C:32]([NH:1][CH2:2][C:3]1[S:4][C:5]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:6][C:7]=1[NH:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=1)=[O:10])=[O:33])([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 27960291-Hydroxybenzotriazole hydrateHCID 18322354HCID 18322354, compound

Product 1

HCID 10277134HCID 10277134, compoundYield 40.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-(2-aminomethyl-5-tert-butyl-3-thienyl)-N′-(4-methylphenyl)urea (0.20 g, 0.63 mmol) and N-carbo-tert-butoxyglycine (0.11 g, 0.63 mmol, 1.0 equiv) in THF (2 mL) at room temp. were added dicyclohexylcarbodiimide (0.13 g, 0.63 mmol, 1.0 equiv) and 1-hydroxybenzotriazole monohydrate (0.008 g, 0.06 mmol, 10 mol %). The resulting mixture was allowed to stir 18 h, diluted with EtOAc (5 mL), and washed with a saturated NaCl solution. The organic layer was dried (MgSO4) and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient from 30% EtOAc/hexane to 50% EtOAc/hexane) to afford N-(2-(N-(N-carbo-tert-butoxyglycyl)aminomethyl)-5-tert-butyl-3-thienyl)-N′-(4-methylphenyl)urea (0.12 g, 40%, Example 52): mp 174-176° C.; 1H NMR (CDCl3) δ1.38 (s, 9H), 2.27 (m, 3H), 4.38 (m, 2H), 6.67 (bs, 1H), 6.89 (m, 1H), 7.27 (m, 1H), 7.33 (m, 2H), 8.58 (bs, 1H); FAB-LRMS m/z 475 (M+H).

Workup

  1. washwashed with a saturated NaCl solution
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by flash chromatography (gradient from 30% EtOAc/hexane to 50% EtOAc/hexane)

Sources & evidence

ORD record
ord-549ba48b04d44531be417befc7378778
Source dataset
uspto-grants-2002_02
Patent number
US06344476B1

Reaction notes

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