Dimethylformamide → HCID 118062828, compound

HRID 920786Notes

Reaction equation

HRID 920786 reaction equation
[F:1][CH:2]([F:12])[C:3]1(C(O)=O)[CH2:6][C:5]([F:8])([F:7])[CH2:4]1.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[Cl:30][C:31]1[CH:32]=[C:33]([C:38]2[C:46]([C:47]([NH2:49])=[O:48])=[C:41]3[CH2:42][NH:43][CH2:44][CH2:45][N:40]3[N:39]=2)[CH:34]=[CH:35][C:36]=1[F:37].C[N:51]([CH:53]=[O:54])C>C1(C)C=CC=CC=1>[Cl:30][C:31]1[CH:32]=[C:33]([C:38]2[C:46]([C:47]([NH2:49])=[O:48])=[C:41]3[CH2:42][N:43]([C:53]([NH:51][C:3]4([CH:2]([F:1])[F:12])[CH2:4][C:5]([F:7])([F:8])[CH2:6]4)=[O:54])[CH2:44][CH2:45][N:40]3[N:39]=2)[CH:34]=[CH:35][C:36]=1[F:37]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 199401P,P-Diphenylphosphinic azideHCID 1180616272-(3-Chloro-4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-3-carboxamideHCID 1180617751773508-58-9

Product 1

HCID 118062828HCID 118062828, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of Intermediate 304E (26.3 mg, 0.141 mmol) in toluene (3 mL) was added TEA (0.090 mL, 0.643 mmol) and DPPA (0.059 mL, 0.257 mmol) and the resulting solution was heated at 85° C. for 1 h. The reaction mixture was cooled to RT and to it was added a solution of Intermediate 185B (40 mg, 0.129 mmol) in DMF (1 mL) and stirred at RT for 8 h. It was concentrated and the residue was extracted with ethyl acetate (3×10 mL). The combined organic layer was dried over sodium sulfate, filtered and the filtrate concentrated. The crude product was further purified by preparative HPLC to afford Compound 304 as an off-white solid (18 mg, 28%). HPLC retention times 1.57 min. and 1.59 min. (Methods E and L respectively). ES(MS): m/z=478 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.90 (d, J=1.5 Hz, 1H), 7.72-7.63 (m, 3H), 7.45-7.21 (m, 2H), 6.47-6.11 (m, 1H), 4.77 (s, 2H), 4.17 (t, J=5.3 Hz, 2H), 3.88 (t, J=5.3 Hz, 2H), 3.06-2.91 (m, 2H), 2.90-2.76 (m, 2H).

Workup

  1. temperatureThe reaction mixture was cooled to RT and to it
  2. concentrationIt was concentrated
  3. extractionthe residue was extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated
  7. customThe crude product was further purified by preparative HPLC

Sources & evidence

ORD record
ord-a6f57b35003a460d8953db389f308ebb
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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