Trifluoroacetic acid → HCID 136348453, compound

HRID 1748806Notes

Reaction equation

HRID 1748806 reaction equation
C(O)(C(F)(F)F)=O.[Br:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]([C:20]2[C:21]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=3)=[N:22][N:23]([CH2:33][CH3:34])[C:24]=2[NH:25]C(=O)OC(C)(C)C)[CH2:16][CH2:17][CH:18]=O)=[CH:11][CH:10]=1.BrC1C=CC(C2CCC=NC3N(CC)N=C(C4C=CC=CN=4)C2=3)=CC=1.[Na]>O.C(#N)C.C(Cl)Cl>[Br:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:16][CH2:17][CH2:18][NH:25][C:24]3[N:23]([CH2:33][CH3:34])[N:22]=[C:21]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][N:36]=4)[C:20]2=3)=[CH:11][CH:10]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 5360545SodiumHCID 86724134HCID 86724134, compoundHCID 86724136HCID 86724136, compound

Product 1

HCID 136348453HCID 136348453, compoundYield 77%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

TFA (0.800 mL) was added to a solution of tert-butyl (4-(1-(4-bromophenyl)-4-oxobutyl)-1-ethyl-3-(pyridin-2-yl)-1H-pyrazol-5-yl)carbamate (0.0400 g, 0.0780 mmol) and DCM (0.800 mL). After about 40 min, reaction monitor by LC-MS (Table 1, Method g) Rt=2.68 min; m/z 395 and 397 (M+H)+indicated conversion to 4-(4-bromophenyl)-1-ethyl-3-(pyridin-2-yl)-1,4,5,6-tetrahydropyrazolo[3,4-b]azepine. Sodium triacetoxyhydroborate (0.083 g, 0.390 mmol) was added in one portion. After about 45 min, the volatiles were removed under reduced pressure. THF (0.8 mL) and 2 M aqueous HCl (0.8 mL) were added. After about 15 min, saturated aqueous NaHCO3 (5 mL) was added. The solution was extracted with EtOAc (2×5 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel (4 g) using a gradient of 50-100% EtOAc in heptane. The fractions containing product were combined and concentrated under reduced pressure to afford an ivory solid. Acetonitrile (0.5 mL) was added. The slurry was diluted with water (4 mL) then sonicated for about 2 min. The organic volatiles were removed under reduced pressure. The mixture was frozen then lyophilized to afford 4-(4-bromophenyl)-1-ethyl-3-(pyridin-2-yl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-b]azepine (0.0239 g, 0.0600 mmol, 77%) as an ivory solid. LC-MS (Table 1, Method h) Rt=2.61 min; m/z 397 and 399 (M+H)+; 1H NMR (400 MHz, DMSO) δ 8.44-8.34 (m, 1H), 7.79-7.75 (m, 1H), 7.70-7.63 (m, 1H), 7.35 (d, J=8.4 Hz, 2H), 7.17-7.11 (m, 1H), 7.05 (d, J=8.4 Hz, 2H), 5.56-5.47 (m, 2H), 4.16-3.94 (m, 2H), 3.33-3.20 (m, 1H), 2.81-2.70 (m, 1H), 2.18-2.07 (m, 1H), 1.92-1.80 (m, 1H), 1.71-1.59 (m, 1H), 1.49-1.35 (m, 1H), 1.30 (t, J=7.1 Hz, 3H).

Workup

  1. customreaction monitor by LC-MS (Table 1, Method g) Rt=2.68 min
  2. waitAfter about 45 min
  3. customthe volatiles were removed under reduced pressure
  4. additionTHF (0.8 mL) and 2 M aqueous HCl (0.8 mL) were added
  5. waitAfter about 15 min
  6. additionsaturated aqueous NaHCO3 (5 mL) was added
  7. extractionThe solution was extracted with EtOAc (2×5 mL)
  8. dry with materialThe combined organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified on silica gel (4 g)
  12. additionThe fractions containing product
  13. concentrationconcentrated under reduced pressure
  14. customto afford an ivory solid
  15. customthen sonicated for about 2 min
  16. customThe organic volatiles were removed under reduced pressure
  17. temperatureThe mixture was frozen

Sources & evidence

ORD record
ord-b6cc480b2b1a40869fde09644d4a1d8e
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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