Dimethylcarbamoyl Chloride → HCID 71472665, compound

HRID 925616Notes

Reaction equation

HRID 925616 reaction equation
[OH:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C:7]2[CH:8]=[C:9]3[C:14](=[C:15]4[N:20]([CH3:21])[CH2:19][CH:18]=[CH:17][C:16]=24)[N:13]=[CH:12][N:11]([C@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]2[OH:28])[C:10]3=[O:29])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:39][N:40]([CH3:44])[C:41](Cl)=[O:42]>ClCCl>[CH3:39][N:40]([CH3:44])[C:41](=[O:42])[O:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[CH:8]=[C:9]3[C:14](=[C:15]4[N:20]([CH3:21])[CH2:19][CH:18]=[CH:17][C:16]=24)[N:13]=[CH:12][N:11]([C@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@@H:23]2[OH:28])[C:10]3=[O:29])=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 6598Dimethylcarbamoyl Chloride2×HCID 8471TriethylamineHCID 71042119HCID 71042119, compound

Product 1

HCID 71472665HCID 71472665, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 6-(4-hydroxybenzyl)-3-[(1S,2S)-2-hydroxycyclohexyl]-10-methyl-9,10-dihydropyrido[3,2-h]quinazolin-4(3H)-one (Example 7, 0.025 g, 0.060 mmol) in 2 mL of dichloromethane at 0° C. was added triethylamine (0.012 mL, 0.090 mmol) and dimethyl carbamyl chloride (0.010 g, 0.090 mmol). After 2 h, the mixture was warmed to rt and additional dimethyl carbamyl chloride (0.019 g, 0.18 mmol) was added. After 20 h, the reaction was warmed to 35° C., and after an additional 36 h, diluted with dichloromethane and washed with water and brine. The organic solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-3% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 489.1 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 3.24 (d, J=8.4 Hz, 1H), 8.03 (s, 1H), 7.41-7.38 (m, 1H), 7.14 (d, J=7.9 Hz, 2H), 7.01-6.98 (m, 2H), 4.77-4.64 (m, 2H), 4.37 (s, 2H), 3.64 (br s, 1H), 3.27 (s, 3H), 3.06 (s, 3H), 2.98 (s, 3H), 2.22-2.19 (m, 1H), 2.12-2.09 (m, 1H), 1.91 (br s, 1H), 1.82 (br s, 1H), 1.64-1.60 (m, 1H), 1.49-1.25 (m, 4H).

Workup

  1. waitAfter 20 h
  2. temperaturethe reaction was warmed to 35° C.
  3. waitafter an additional 36 h
  4. washwashed with water and brine
  5. dry with materialThe organic solution was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified via silica gel chromatography
  9. washeluting with 0-3% methanol in dichloromethane

Sources & evidence

ORD record
ord-464e869cc569445aaf789aba2682ccd5
Source dataset
uspto-grants-2016_03
Patent number
US09284312B2

Reaction notes

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