1-Chloroethyl chloroformate → HCID 16660143, compound

HRID 2097090Notes

Reaction equation

HRID 2097090 reaction equation
[CH2:1]([O:3][C:4]1[C:37]([CH:38]([CH3:40])[CH3:39])=[CH:36][CH:35]=[CH:34][C:5]=1[CH2:6][N:7]([CH3:33])[C:8](=[O:32])[CH:9]=[CH:10][C:11]1[CH:31]=[N:30][C:14]2[NH:15][C:16](=[O:29])[CH2:17][N:18](CC3C=CC(OC)=CC=3)[CH2:19][C:13]=2[CH:12]=1)[CH3:2].[Cl:41]C(OC(Cl)C)=O>ClC(Cl)C>[ClH:41].[CH2:1]([O:3][C:4]1[C:37]([CH:38]([CH3:39])[CH3:40])=[CH:36][CH:35]=[CH:34][C:5]=1[CH2:6][N:7]([CH3:33])[C:8](=[O:32])/[CH:9]=[CH:10]/[C:11]1[CH:31]=[N:30][C:14]2[NH:15][C:16](=[O:29])[CH2:17][NH:18][CH2:19][C:13]=2[CH:12]=1)[CH3:2]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 66966598HCID 66966598, compound

Product 1

HCID 16660143HCID 16660143, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of N-(2-ethoxy-3-isopropylbenzyl)-3-[4-(4-methoxybenzyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]-N-methylacrylamide (0.200 g, 0.369 mmol) in dichloroethane (8.0 mL) was cooled in an ice bath and treated with 1-chloroethyl chloroformate (0.044 mL, 0.40 mmol). After stirring at 0° C. under N2 for 30 min and then at room temperature for 30 min, the mixture was heated to reflux for 2 h. The mixture was allowed to cool and then concentrated to dryness. Purification by flash column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 99.5:0.5) gave a white solid (0.128 g, 0.241 mmol). The solid was dissolved in methanol (4 mL) and heated to reflux for 6.5 h. The mixture was allowed to cool and the resulting solid was isolated by filtration, washed with MeOH and Et2O and dried to give the title compound (1.28 g, 46%) as a white powder and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 11.08-11.06 (m, 1H), 9.96 (br s, 2H), 8.77-8.71 (m, 1H), 8.32-8.23 (m, 1H), 7.63-7.55 (m, 1H), 7.40-7.32 (m, 1H), 7.26-7.21 (m, 1H), 7.13-7.04 (m, 1H), 6.91-6.84 (m, 1H), 4.83-4.67 (m, 2H), 4.27-4.22 (m, 2H), 3.88-3.78 (m, 4H), 3.29-2.25 (m, 1H), 3.13-2.89 (m, 3H), 1.40-1.35 (m, 3H), 1.19-1.17 (m, 6H); MS (ESI) m/e 423 (M+H)+.

Workup

  1. temperaturewas cooled in an ice bath
  2. waitat room temperature for 30 min
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 2 h
  5. temperatureto cool
  6. concentrationconcentrated to dryness
  7. customPurification by flash column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 99.5:0.5)

Sources & evidence

ORD record
ord-108ce18c18bb47faaf6015e1c2a4be3d
Source dataset
uspto-grants-2013_05
Patent number
US08450307B2

Reaction notes

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