Trifluoroacetic acid → HCID 58299979, compound

HRID 79160Notes

Reaction equation

HRID 79160 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[N:21]=[CH:20][C:19]([N:22]5[CH2:27][CH2:26][CH:25]([CH2:28][C:29](O)=[O:30])[CH2:24][CH2:23]5)=[CH:18][CH:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:32]=[CH:33][N:34]=[C:35]([F:36])[C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N1C=CN=C1)([N:39]1C=CN=C1)=O.C(O)(C(F)(F)F)=O>CN(C=O)C>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[N:21]=[CH:20][C:19]([N:22]5[CH2:23][CH2:24][CH:25]([CH2:28][C:29]([NH2:39])=[O:30])[CH2:26][CH2:27]5)=[CH:18][CH:17]=4)[N:13]=[CH:14][C:9]=3[C:8]3[CH:32]=[CH:33][N:34]=[C:35]([F:36])[C:7]2=3)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 58299865HCID 58299865, compound

Product 1

HCID 58299979HCID 58299979, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Compound 259 (0.077 g, 0.16 mmol) was suspended in DMF (1.5 mL) and 1,1′-carbonyldiimidazole (0.028 g, 0.17 mmol) was added. The reaction was stirred at 70° C. After 1 h, the suspension was cooled to 0° C. and ammonia gas was sparged therein. The tube was sealed and warmed to 70° C. After 1 h, the reaction was diluted in water (30 mL) and filtered. Purification by reversed phase HPLC (10-90% acetonitrile in water with 0.1% TFA) provided compound 260 (0.025 g, 26% yield) as a TFA salt. 1H NMR (500 MHz, DMSO-d6) δ 1.25-1.39 (m, 2 H) 1.70-1.84 (m, 4 H) 1.89 (dt, J=7.27, 3.58 Hz, 1 H) 2.05 (d, J=7.09 Hz, 4 H) 2.14 (br. s., 2 H) 2.27 (d, J=8.31 Hz, 2 H) 2.80 (t, J=10.88 Hz, 2 H) 3.70 (d, J=12.23 Hz, 2 H) 5.52 (quin, J=9.05 Hz, 1 H) 6.80 (br. s., 1 H) 7.31 (br. s., 1 H) 7.74 (br. s., 1 H) 7.98 (br. s., 1 H) 8.05 (br. s., 1 H) 8.13 (d, J=3.91 Hz, 1 H) 8.21-8.28 (m, 1 H) 9.51 (s, 1 H) 11.36 (br. s., 1 H) ppm.

Workup

  1. temperaturethe suspension was cooled to 0° C.
  2. customammonia gas was sparged
  3. customThe tube was sealed
  4. temperaturewarmed to 70° C
  5. waitAfter 1 h
  6. additionthe reaction was diluted in water (30 mL)
  7. filtrationfiltered
  8. customPurification by reversed phase HPLC (10-90% acetonitrile in water with 0.1% TFA)

Sources & evidence

ORD record
ord-817664e6dbb24eeebd7f84162e4b984e
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

Loading…