Dichloromethane → HCID 178473899, compound

HRID 592030Notes

Reaction equation

HRID 592030 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[NH:41][C:24]4=[N:25][CH:26]=[C:27]([Cl:40])[C:28]([NH:29][C@H:30]5[C@@H:35]([C:36](=[O:38])[NH2:37])[C@H:34]6[CH2:39][C@@H:31]5[CH:32]=[CH:33]6)=[C:23]4[N:22]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[CH2:42](Cl)Cl.FC(F)(F)C(O)=O.C(OC(=O)C)(=O)C.C(N(CC)CC)C.C(N(CC)CC)C>C(Cl)Cl.C1COCC1>[C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[NH:41][C:24]4=[N:25][CH:26]=[C:27]([Cl:40])[C:28]([NH:29][C@@H:30]5[C@@H:31]6[CH2:39][C@@H:34]([CH:33]=[CH:32]6)[C@@H:35]5[C:36]([NH2:37])=[O:38])=[C:23]4[N:22]=3)=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)(=[O:5])[CH3:42]

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 22592508triethylamine TriethylamineHCID 178452299HCID 178452299, compound

Product 1

HCID 178473899HCID 178473899, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

[4-{4-[7-((1R,2R,3S,4S)-3-Carbamoyl-bicyclo[2.2.1]hept-5-en-2-ylamino)-6-chloro-3H-imidazo[4,5-b]pyridin-2-yl]-benzyl}-piperazine-1-carboxylic acid tert-butyl ester (159.0 mg, 0.2750 mmol) was taken up into Methylene chloride (8.4 mL, 130 mmol) and treated with Trifluoroacetic Acid (3 mL, 40 mmol) and stirred @ 40° C., O/N. The solution was then concentrated. The residue was taken up into methanol and treated with 900 mg mp carbonate for ½ hour. The resin was removed by filtration and filtrate concentrated. The residue was taken up into DCM/THF (˜30 mL) and Acetic anhydride (0.56 mL, 5.9 mmol) was added followed by triethylamine Triethylamine (0.56 mL, 4.0 mmol). Solution was stirred at RT for 1 hr and then concentrated. The residue was purified via reverse phase chromotography using a gradient of MeCN with 0.1% TFA in Water with 0.1% TFA on a Phenomenex Gemini-NX C18 AXIA column. Fractions containing desired product were poured into sat'd sodium bicarbonate and extracted with 3 portions of methylene chloride. The combined organic was dried over magnesium sulfate, filtered and evaporated to yield a yellow solid, 15.00 mg, 10% yield. (300 MHz, DMSO-d6) 13.26 (s, 1H), 8.10 (d, J=8 Hz, 2H), 7.95 (s, 1H), 7.78 (m, 1H), 7.48 (d, J=8 Hz, 2H), 7.22 (m, 2H), 6.44-6.33 (m, 2H), 5.17 (t, J=17 Hz, 9 Hz, 1H), 3.56 (s, 2H), 3.43 (m, 4H), 2.89 (s, 1H), 2.80 (s, 1H), 2.62 (d, J=9 Hz, 1H), 2.40 (m, 2H), 2.33 (m, 2H), 2.25 (d, J=8 Hz, 1H), 1.98 (s, 3H), 1.38 (d, J=8 Hz, 1H). MS=521 (M+H), HPLC: 1.47 min. (G Method)

Workup

  1. concentrationThe solution was then concentrated
  2. additiontreated with 900 mg mp carbonate for ½ hour
  3. customThe resin was removed by filtration and filtrate
  4. concentrationconcentrated
  5. additionwas added
  6. stirringSolution was stirred at RT for 1 hr
  7. concentrationconcentrated
  8. customThe residue was purified via reverse phase chromotography
  9. additionFractions containing desired product
  10. additionwere poured into sat'd sodium bicarbonate
  11. extractionextracted with 3 portions of methylene chloride
  12. dry with materialThe combined organic was dried over magnesium sulfate
  13. filtrationfiltered
  14. customevaporated
  15. customto yield a yellow solid, 15.00 mg, 10% yield
  16. custom1.47 min. (G Method)

Sources & evidence

ORD record
ord-6cf45fa7a4fc4a5aa9efb4eac159156d
Source dataset
uspto-grants-2016_01
Patent number
US09238656B2

Reaction notes

Loading…