Triethylamine → HCID 58468021, compound

HRID 1879388Notes

Reaction equation

HRID 1879388 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[C:8]2=[O:24])[CH2:3][CH2:2]1.C(N(CC)CC)C.Cl[C:33](OC(Cl)(Cl)Cl)=[O:34].[NH2:40][C@H:41]1[C:47]2=[N:48][CH:49]=[CH:50][CH:51]=[C:46]2[C@@H:45]([NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])[C@H:44]([C:60]2[CH:65]=[CH:64][CH:63]=[C:62]([F:66])[C:61]=2[F:67])[CH2:43][CH2:42]1>C(Cl)Cl.O1CCCC1.C(OCC)(=O)C>[F:67][C:61]1[C:62]([F:66])=[CH:63][CH:64]=[CH:65][C:60]=1[C@@H:44]1[CH2:43][CH2:42][C@@H:41]([NH:40][C:33]([N:1]2[CH2:6][CH2:5][CH:4]([N:7]3[C:15]4[C:10](=[N:11][CH:12]=[CH:13][CH:14]=4)[N:9]([CH2:16][O:17][CH2:18][CH2:19][Si:20]([CH3:21])([CH3:23])[CH3:22])[C:8]3=[O:24])[CH2:3][CH2:2]2)=[O:34])[C:47]2=[N:48][CH:49]=[CH:50][CH:51]=[C:46]2[C@H:45]1[NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56]

Participants

8

Reactant 4

HCID 8471Triethylamine3×HCID 10426DiphosgeneHCID 57911432HCID 57911432, compoundHCID 58467980HCID 58467980, compound

Product 1

HCID 58468021HCID 58468021, compoundYield 15.7%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-20 °C

Procedure

In an oven-dried 100 ml round-bottom flask was dissolved 1-(piperidin-4-yl)-3-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one (52.3 mg, 0.150 mmol) in methylene chloride (5 mL) to give a colorless solution. Triethylamine (0.038 mL, 0.28 mmol) was added under nitrogen and the mixture was cooled to −20° C. Trichloromethyl chloroformate (0.012 mL, 0.100 mmol) was added dropwise. The mixture was gradually warmed up with stirring to 10° C. for 1 h, during which time the solution became slightly yellow. The reaction was concentrated to dryness under vacuum. tert-Butyl (5S,6S,9R)-9-amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-ylcarbamate (48.7 mg, 0.125 mmol) and triethylamine (0.038 mL, 0.275 mmol) dissolved in 1 mL tetrahydrofuran (plus 2 mL rinse) was added via cannula at room temperature. More triethylamine (0.038 mL, 0.275 mmol) was added. The resulting faint yellow suspension was stirred under nitrogen overnight. The reaction was diluted with ethyl acetate and washed with water three times. The ethyl acetate layer was separated, dried (sodium sulfate), filtered and concentrated. Flash chromatography using methanol in methylene chloride from 0 to 10% gave the desired product (12 mg, 13%): MS(ESI)[M+H+]=764.38.

Workup

  1. customto give a colorless solution
  2. temperatureThe mixture was gradually warmed up
  3. concentrationThe reaction was concentrated to dryness under vacuum
  4. wash(plus 2 mL rinse)
  5. additionwas added via cannula at room temperature
  6. stirringThe resulting faint yellow suspension was stirred under nitrogen overnight
  7. washwashed with water three times
  8. customThe ethyl acetate layer was separated
  9. dry with materialdried (sodium sulfate)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-800fafa01b3849488a0a371adbdc6d7a
Source dataset
uspto-grants-2012_11
Patent number
US08314117B2

Reaction notes

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