Tetrahydrofuran → HCID 118061610, compound

HRID 920800Notes

Reaction equation

HRID 920800 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2(C(O)=O)[CH2:12][C:11]([F:14])([F:13])[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].C1C=CC(P([N:32]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:35][C:36]1[CH:37]=[C:38]([C:43]2[C:51]([C:52]([NH2:54])=[O:53])=[C:46]3[CH2:47][NH:48][CH2:49][CH2:50][N:45]3[N:44]=2)[CH:39]=[CH:40][C:41]=1[F:42].C1[CH2:59][O:58]CC1>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:35][C:36]1[CH:37]=[C:38]([C:43]2[C:51]([C:52]([NH2:54])=[O:53])=[C:46]3[CH2:47][N:48]([C:59]([NH:32][C:9]4([C:6]5[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=5)[CH2:10][C:11]([F:13])([F:14])[CH2:12]4)=[O:58])[CH2:49][CH2:50][N:45]3[N:44]=2)[CH:39]=[CH:40][C:41]=1[F:42]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 199401P,P-Diphenylphosphinic azideHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamideHCID 118061706HCID 118061706, compound

Product 1

HCID 118061610HCID 118061610, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of Intermediate 314F (36.2 mg, 0.153 mmol) in toluene (1 mL) was added TEA (0.071 mL, 0.509 mmol), DPPA (0.044 mL, 0.204 mmol) and the reaction mixture was heated to 85° C. and stirred for 1 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 (0.5 mL) and stirred at RT for 12 h. The reaction mixture was diluted with EtOAc (10 mL), washed successively with water, a 10% aq. solution of NaHCO3 and brine, then dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative HPLC to afford Compound 314 as an off-white solid (0.017 g, 32%). HPLC retention times 1.604 min. and 1.605 min. (Methods E and L respectively). MS(ES): m/z=529.2 [M+H]+; 1H NMR: (400 MHz, DMSO-d6) δ ppm 7.92 (s, 1H), 7.86-7.77 (m, 3H), 7.67 (ddd, J=8.7, 4.9, 2.0 Hz, 1H), 7.64-7.58 (m, 2H), 7.50-7.41 (m, 1H), 7.36 (br. s., 1H), 7.18 (br. s., 1H), 4.73 (s, 2H), 4.14 (t, J=5.3 Hz, 2H), 3.84 (t, J=5.3 Hz, 2H), 3.17 (t, J=12.3 Hz, 4H).

Workup

  1. temperatureThe reaction mixture was cooled to RT and to it
  2. stirringstirred at RT for 12 h
  3. washwashed successively with water
  4. dry with materiala 10% aq. solution of NaHCO3 and brine, then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-3d23459f868040c39883e347dfd99b13
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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