1-Chloroethyl chloroformate → HCID 10342385, compound

HRID 1711869Notes

Reaction equation

HRID 1711869 reaction equation
COC1C=CC(C[N:8]2[CH2:14][C:13]3[CH:15]=[C:16](/[CH:19]=[CH:20]/[C:21]([N:23]([CH3:35])[CH2:24][C:25]4[N:26]([CH3:34])[C:27]5[C:32]([CH:33]=4)=[CH:31][CH:30]=[CH:29][CH:28]=5)=[O:22])[CH:17]=[N:18][C:12]=3[NH:11][C:10](=[O:36])[CH2:9]2)=CC=1.[Cl:39]C(OC(Cl)C)=O>ClC(Cl)C.CO.C(Cl)Cl>[ClH:39].[CH3:35][N:23]([CH2:24][C:25]1[N:26]([CH3:34])[C:27]2[C:32]([CH:33]=1)=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21](=[O:22])/[CH:20]=[CH:19]/[C:16]1[CH:17]=[N:18][C:12]2[NH:11][C:10](=[O:36])[CH2:9][NH:8][CH2:14][C:13]=2[CH:15]=1

Participants

6

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 10482563HCID 10482563, compound

Product 1

HCID 10342385HCID 10342385, compoundYield 49%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (E)-3-[4-(4-methoxy-benzyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]-N-methyl-N-(1-methyl-1H-indol-2-ylmethyl)acrylamide (2.00 g, 3.92 mmol), from Example 65, in dichloroethane (80 mL) was cooled in an ice bath and treated with 1-chloroethyl chloroformate (0.47 mL, 4.31 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 1.5 h. The mixture was allowed to cool and then concentrated to dryness. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3) gave a tan solid. The solid was suspended in methanol and heated to reflux for 2 h. The mixture was allowed to cool and the solid was isolated by filtration, dissolved in CH2Cl2, washed with 1 N NaOH, dried over Na2SO4, filtered and the solvent was removed in vacuo. Purification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3 to 95:5) gave the title compound (0.70 g, 49%) as an off-white solid: 1H NMR (300 MHz, CDCl3) δ 8.38-8.33 (m, 2H), 7.72-7.67 (m, 1H), 7.60-7.57 (m, 2H), 7.32-7.20 (m, 3H), 7.14-7.09 (m, 1H), 6.90-6.80 (m, 1H), 6.49-6.38 (m, 1H), 4.93-4.78 (m, 2H), 4.08 (s, 2H), 3.95 (s, 2H), 3.71 (s, 3H), 3.13-3.07 (m, 3H); MS (ESI) m/e 390 (M+H)+.

Workup

  1. waitat room temperature for 30 min
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 1.5 h
  4. temperatureto cool
  5. concentrationconcentrated to dryness
  6. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3)
  7. customgave a tan solid
  8. temperatureheated
  9. temperatureto reflux for 2 h
  10. temperatureto cool
  11. customthe solid was isolated by filtration
  12. washwashed with 1 N NaOH
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. customthe solvent was removed in vacuo
  16. customPurification by flash column chromatography (silica gel, CH2Cl2/MeOH, 97:3 to 95:5)

Sources & evidence

ORD record
ord-87eeb86141644fd2a34f5b67f2daad19
Source dataset
uspto-grants-2010_09
Patent number
US07790709B2

Reaction notes

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