Tetrahydrofuran → HCID 59619952, compound

HRID 445663Notes

Reaction equation

HRID 445663 reaction equation
OC(C(F)(F)F)=O.[CH3:8][O:9][C:10]1[N:15]=[CH:14][C:13]([C:16]2[CH:25]=[CH:24][C:23]3[N:22]=[CH:21][C:20]4[N:26]([CH3:40])[C:27](=[O:39])[N:28]([C:29]5[C:30]([CH3:38])=[N:31][N:32]([CH2:34][C:35]([OH:37])=O)[CH:33]=5)[C:19]=4[C:18]=3[CH:17]=2)=[CH:12][CH:11]=1.[B-](F)(F)(F)F.[CH3:46][N:47](C(ON1C(=O)C=CC=C1)=[N+](C)C)[CH3:48].CCN(C(C)C)C(C)C.C1COCC1>CC(N(C)C)=O>[CH3:8][O:9][C:10]1[N:15]=[CH:14][C:13]([C:16]2[CH:25]=[CH:24][C:23]3[N:22]=[CH:21][C:20]4[N:26]([CH3:40])[C:27](=[O:39])[N:28]([C:29]5[C:30]([CH3:38])=[N:31][N:32]([CH2:34][C:35]([N:47]([CH3:48])[CH3:46])=[O:37])[CH:33]=5)[C:19]=4[C:18]=3[CH:17]=2)=[CH:12][CH:11]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 131730678HCID 131730678, compound

Product 1

HCID 59619952HCID 59619952, compound

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of {4-[8-(6-Methoxy-pyridin-3-yl)-3-methyl-2-oxo-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl]-3-methyl-pyrazol-1-yl}-acetic acid TFA salt (Example 101, 60 mg, 0.107 mmol), TPTU (128 mg, 0.430 mmol) and DIPEA (0.094 ml, 0.537 mmol) in DMA (1.5 ml) was stirred under argon at rt for 20 min. Then dimethtylamine in THF 2 M (Aldrich, Buchs, Switzerland, 0.242 ml, 0.483 mmol) was added and the RM was stirred at rt for 3 h. The RM was directly purified by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 50:50). The fractions containing products were collected together and basified with NaHCO3 (0.3 g), before being concentrated. The resulting layer was extracted with EtOAc, washed with brine, dried over Na2SO4, filtered and evaporated to dryness to give the title compound as a white solid. (HPLC: tR 2.57 min (Method A); M+H=472 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.95 (s, 1H), 8.50-8.43 (m, 1H), 8.14-8.04 (m, 2H), 8.01-7.96 (m, 1H), 7.95-7.90 (m, 1H), 7-77-7.71 (m, 1H), 6.87-6.81 (m, 1H), 5.25-5.09 (m, 2H), 3.86 (s, 3H), 3.56 (s, 3H), 3.05 (s, 3H), 2.88 (s, 3H), 1.93 (s, 3H))

Workup

  1. stirringthe RM was stirred at rt for 3 h
  2. customThe RM was directly purified by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 50:50)
  3. additionThe fractions containing products
  4. customwere collected together
  5. concentrationbefore being concentrated
  6. extractionThe resulting layer was extracted with EtOAc
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-59b7283253c94e189fddd4eff733419c
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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