2-Bromopropanedial → tert-Butyl 3-(5-formylthiazol-2-ylamino)propylcarbamate

HRID 1755462Notes

Reaction equation

HRID 1755462 reaction equation
[NH:1]([CH2:5][CH2:6][CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:2]([NH2:4])=[S:3].C([O-])(=O)C.[Na+].Br[CH:22]([CH:25]=O)[CH:23]=[O:24]>C1COCC1.C(O)(=O)C>[CH:23]([C:22]1[S:3][C:2]([NH:1][CH2:5][CH2:6][CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[N:4][CH:25]=1)=[O:24]

Participants

6

Reactant 3

HCID 749452-BromopropanedialHCID 517045Sodium AcetateHCID 20616909tert-Butyl 3-thioureidopropylcarbamate

Product 1

HCID 86700109tert-Butyl 3-(5-formylthiazol-2-ylamino)propylcarbamateYield 33%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of material from Example 59 (3.4 g, 10.20 mmol) in a mixture of THF (30 mL) and acetic acid (5.00 mL) is added sodium acetate (1.004 g, 12.24 mmol) followed by 2-bromomalonaldehyde (1.540 g, 10.20 mmol). The resulting mixture is stirred at room temp for 18 h, then filtered thru a ground glass frit and the filtrate is concentrated in vacuo. The resulting residue treated with EtOAc, filtered thru a ground glass frit and the filtrate is extracted with sodium bicarbonate, water, brine, dried over Na2SO4, filtered and evaporated to dryness. The residue is purified by BIOTAGE® Silica gel chromatography on an 80 g Thompson Single Step silica cartridge using a linear gradient from 30% EtOAc/hexanes to 100% EtOAc over 11.25 column volumes to give 960 mg (29.7%) of the title compound as a yellow solid. LC/MS (Condition A): ret. T=2.92 min, (M+Na)+ 308.13. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.64 (1 H, s), 8.83-8.98 (1 H, m), 8.06 (1 H, s), 6.89 (1 H, t, J=5.40 Hz), 3.31 (2 H, d, J=5.27 Hz), 2.99 (2 H, q, J=6.69 Hz), 1.69 (2 H, t, J=7.03 Hz), 1.39 (9 H, s).

Workup

  1. filtrationfiltered thru a ground glass frit
  2. concentrationthe filtrate is concentrated in vacuo
  3. additionThe resulting residue treated with EtOAc
  4. filtrationfiltered thru a ground glass frit
  5. extractionthe filtrate is extracted with sodium bicarbonate, water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe residue is purified by BIOTAGE® Silica gel chromatography on an 80 g Thompson Single Step silica cartridge

Sources & evidence

ORD record
ord-373d74655785478e9d63230cc7fb66c6
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

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