Tetrahydrofuran → HCID 118061452, compound

HRID 920789Notes

Reaction equation

HRID 920789 reaction equation
[F:1][C:2]1([CH3:10])[CH2:5][C:4]([CH3:9])(C(O)=O)[CH2:3]1.C1C=CC(P([N:25]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:28][C:29]1[CH:30]=[C:31]([C:36]2[C:44]([C:45]([NH2:47])=[O:46])=[C:39]3[CH2:40][NH:41][CH2:42][CH2:43][N:38]3[N:37]=2)[CH:32]=[CH:33][C:34]=1[F:35].C1[CH2:52][O:51]CC1>C1(C)C=CC=CC=1.O>[Cl:28][C:29]1[CH:30]=[C:31]([C:36]2[C:44]([C:45]([NH2:47])=[O:46])=[C:39]3[CH2:40][N:41]([C:52]([NH:25][C:4]4([CH3:9])[CH2:3][C:2]([F:1])([CH3:10])[CH2:5]4)=[O:51])[CH2:42][CH2:43][N:38]3[N:37]=2)[CH:32]=[CH:33][C:34]=1[F:35]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 199401P,P-Diphenylphosphinic azideHCID 115011681HCID 115011681, compoundHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamide

Product 1

HCID 118061452HCID 118061452, compoundYield 17%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of Intermediate 307B (29.8 mg, 0.204 mmol) in toluene (2 mL) were added TEA (0.043 mL, 0.305 mmol), DPPA (0.058 mL, 0.254 mmol) and the reaction mixture was heated at 60° C. and stirred for 2 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (30 mg, 0.102 mmol) in THF (1 mL) and stirred for 12 h. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (2×25 mL). The combined organic layer was washed with brine, dried over Na2SO4, filtered and the filtrate concentrated. The crude product was purified by preparative HPLC to afford Compound 307 as an off-white solid (7.55 mg, 17%). HPLC retention time 5.901 min. and 8.366 min. (Methods A and B respectively). MS(ES): m/z=438 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.85 (dd, J=7.0, 2.0 Hz, 1H), 7.68 (ddd, J=8.5, 4.8, 2.3 Hz, 1H), 7.46 (t, J=9.0 Hz, 1H), 7.36 (br. s., 1H), 7.20 (br. s., 1H), 6.88 (s, 1H), 4.71 (s, 2H), 4.12 (t, J=5.3 Hz, 2H), 3.82 (t, J=5.3 Hz, 2H), 2.44 (m, 2H), 2.29-2.17 (m, 2H), 1.46 (d, J=10.8 Hz, 3H), 1.43 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to RT and to it
  2. stirringstirred for 12 h
  3. extractionextracted with ethyl acetate (2×25 mL)
  4. washThe combined organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated
  8. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-fbe90e2e3737431b9b4e03389de6ecd7
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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