Water → HCID 53241941, compound

HRID 1023617Notes

Reaction equation

HRID 1023617 reaction equation
[CH3:1][C:2]([CH3:25])([CH3:24])[C@H:3]([C:5]([NH:7][C:8]1[CH:9]=[N:10][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([O:22][CH3:23])[CH:16]=2)=[CH:12][CH:13]=1)=[O:6])[NH2:4].C(N(CC)CC)C.Cl[C:34](Cl)([O:36]C(=O)OC(Cl)(Cl)Cl)Cl.O>ClCCl>[CH3:1][C:2]([C@H:3]1[NH:4][C:34](=[O:36])[N:7]([C:8]2[CH:9]=[N:10][C:11]([O:14][C:15]3[CH:20]=[CH:19][C:18]([CH3:21])=[C:17]([O:22][CH3:23])[CH:16]=3)=[CH:12][CH:13]=2)[C:5]1=[O:6])([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 94429TriphosgeneHCID 68322502HCID 68322502, compound2×

Product 1

HCID 53241941HCID 53241941, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

3-methyl-N1-(6-{[4-methyl-3-(methyloxy)phenyl]oxy}-3-pyridinyl)-D-valinamide (Intermediate 97, 5.2 mg) was dissolved in dry dichloromethane (0.5 mL). The reaction mixture was cooled down in an ice bath. Triethylamine (12.6 μl, 0.091 mmol) was added at 0° C. Then 0.5 mL of a solution of triphosgene in dry dichloromethane (2.47 mg, 0.0083 mmol) was added dropwise. The reaction mixture was stirred under argon during 20 min at 0° C. Some water was added and the aqueous layer was extracted with dichloromethane 4 times. After drying over sodium sulphate, the solvents were removed under vacuum. The residue obtained was purified by flash chromatography on silica gel (Companion system, 4 g silica cartridge) with cyclohexane/ethylacetate as eluents from 100/0 to 60/40 during 15 min and 60/40 during 10 min. This afforded the title compound (5.9 mg).

Workup

  1. temperatureThe reaction mixture was cooled down in an ice bath
  2. extractionthe aqueous layer was extracted with dichloromethane 4 times
  3. dry with materialAfter drying over sodium sulphate
  4. customthe solvents were removed under vacuum
  5. customThe residue obtained
  6. customwas purified by flash chromatography on silica gel (Companion system, 4 g silica cartridge) with cyclohexane/ethylacetate as eluents from 100/0 to 60/40 during 15 min
  7. wait60/40 during 10 min

Sources & evidence

ORD record
ord-301d40aa97724f9490bd3a115b0232c4
Source dataset
uspto-grants-2014_05
Patent number
US08722695B2

Reaction notes

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