Tetrahydrofuran → HCID 118061732, compound

HRID 920794Notes

Reaction equation

HRID 920794 reaction equation
[F:1][C:2]1([F:16])[CH2:5][C:4]([C:9]2[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=2)(C(O)=O)[CH2:3]1.C1C=CC(P([N:31]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:34][C:35]1[CH:36]=[C:37]([C:42]2[C:50]([C:51]([NH2:53])=[O:52])=[C:45]3[CH2:46][NH:47][CH2:48][CH2:49][N:44]3[N:43]=2)[CH:38]=[CH:39][C:40]=1[F:41].C1[CH2:58][O:57]CC1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:34][C:35]1[CH:36]=[C:37]([C:42]2[C:50]([C:51]([NH2:53])=[O:52])=[C:45]3[CH2:46][N:47]([C:58]([NH:31][C:4]4([C:9]5[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=5)[CH2:3][C:2]([F:1])([F:16])[CH2:5]4)=[O:57])[CH2:48][CH2:49][N:44]3[N:43]=2)[CH:38]=[CH:39][C:40]=1[F:41]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 199401P,P-Diphenylphosphinic azideHCID 1054874861773508-66-9HCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamide

Product 1

HCID 118061732HCID 118061732, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A stirred solution of Intermediate 308E (62.5 mg, 0.271 mmol) in toluene (2 mL) was added TEA (0.057 mL, 0.407 mmol), DPPA (0.062 mL, 0.271 mmol) and the reaction mixture was heated to 70° C. for 2 h. The reaction mass was cooled to RT and to it was added a solution of Intermediate 185B (40 mg, 0.136 mmol) in THF (1 mL) and the reaction mixture was stirred at RT for 12 h. The reaction mass was diluted with ethyl acetate (5 mL), the organic layer was separated, washed with a 10% aq. NaHCO3 solution, water, brine, dried over Na2SO4, filtered and the filtrate concentrated under vacuum. The crude compound was purified by preparative HPLC to afford Compound 308 as a pale yellow solid (54 mg, 75%). The HPLC Retention times are 2.339 min. and 2.344 min. (Methods J and K respectively); MS(ES): −m/z=522 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.82-7.88 (m, 1H), 7.77-7.82 (m, 1H), 7.61-7.72 (m, 1H), 7.47 (s, 3H), 7.30-7.41 (m, 1H), 7.14 (s, 3H), 4.72 (s, 2H), 4.08-4.18 (m, 2H), 3.78-3.88 (m, 2H), 3.10-3.22 (m, 4H).

Workup

  1. temperatureThe reaction mass was cooled to RT and to it
  2. customthe organic layer was separated
  3. washwashed with a 10% aq. NaHCO3 solution, water, brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated under vacuum
  7. customThe crude compound was purified by preparative HPLC

Sources & evidence

ORD record
ord-ed00550d7db3427b9bd276b65c619a6d
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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