Trifluoroacetic acid → HCID 56967632, compound

HRID 1428252Notes

Reaction equation

HRID 1428252 reaction equation
C[Si](C)(C)CCOC[N:7]1[C:11]2[N:12]=[CH:13][N:14]=[C:15]([N:16]3[CH:24]4[CH:19]([N:20]([C:25]([O:27][CH2:28][C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=5)=[O:26])[CH2:21][CH2:22][CH2:23]4)[CH2:18][CH2:17]3)[C:10]=2[CH:9]=[CH:8]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[N:12]1[C:11]2[NH:7][CH:8]=[CH:9][C:10]=2[C:15]([N:16]2[CH:24]3[CH:19]([N:20]([C:25]([O:27][CH2:28][C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[O:26])[CH2:21][CH2:22][CH2:23]3)[CH2:18][CH2:17]2)=[N:14][CH:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86694431HCID 86694431, compound

Product 1

HCID 56967632HCID 56967632, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of the product of Step 2 (2.77 g, 5.46 mmol) in DCM (28 mL) was added TFA (28 mL). The resulting solution was stirred for 1 hour at room temperature. Heptanes were then added, and the mixture was concentrated in vacuo, azeotroping with DCM and heptanes until a constant weight was achieved. The resulting oil was taken up into acetonitrile (28 mL), and ammonium hydroxide (28 mL) was added. The solution was stirred at ambient temperature for approximately 5 minutes, then the reaction mixture was scratched with a glass pipette in order to promote crystallization. The reaction mixture was stirred for approximately 19 hours before being heated at 50° C. for 1 hour. The reaction mixture was cooled, and diluted with water (28 mL). The solids were filtered and the filter cake was rinsed with water and dried under high vacuum until constant weight was achieved to afford the desired product as an off-white solid. LRMS calc'd for C21H24N5O2 [M+H]+, 378; found 378. 1H NMR (500 MHz, DMSO-D6) δ 11.6 (s, 1H), 8.06 (s, 1H), 7.40-7.28 (br m, 5H), 7.10 (s, 1H), 6.52 (s, 1H), 5.13-5.07 (m, 2H), 4.61 (br s, 1H), 4.32 (br s, 1H), 3.98-3.64 (br m, 3H), 2.98-2.80 (m, 1H), 2.36-2.12 (br m, 2H), 2.04 (br m, 1H), 1.64 (br m, 1H), 1.50-1.22 (br m, 2H). Jak1 activity: ++.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customazeotroping with DCM and heptanes until a constant weight
  3. additionwas added
  4. stirringThe solution was stirred at ambient temperature for approximately 5 minutes
  5. customcrystallization
  6. stirringThe reaction mixture was stirred for approximately 19 hours
  7. temperaturebefore being heated at 50° C. for 1 hour
  8. temperatureThe reaction mixture was cooled
  9. additiondiluted with water (28 mL)
  10. filtrationThe solids were filtered
  11. washthe filter cake was rinsed with water
  12. customdried under high vacuum until constant weight

Sources & evidence

ORD record
ord-beaaba06a53445cf967da63155aeea94
Source dataset
uspto-grants-2015_01
Patent number
US08937077B2

Reaction notes

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