Diisopropylethylamine → HCID 178520721, compound

HRID 2378706Notes

Reaction equation

HRID 2378706 reaction equation
[Br:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][C:22]([F:25])([F:24])[F:23])[C:13](=[O:20])[C@H:14]([CH2:16][C:17](O)=[O:18])[CH2:15][C:8]=3[CH:7]=[C:6]([Br:26])[C:5]=2[NH:4][N:3]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl.[NH:59]1[CH2:64][CH2:63][CH:62]([C:65]2[C:66](=[O:75])[NH:67][C:68]3[C:73]([CH:74]=2)=[CH:72][CH:71]=[CH:70][CH:69]=3)[CH2:61][CH2:60]1>CN(C)C=O>[Br:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][C:22]([F:25])([F:23])[F:24])[C:13](=[O:20])[C@H:14]([CH2:16][C:17](=[O:18])[N:59]4[CH2:60][CH2:61][CH:62]([C:65]5[C:66](=[O:75])[NH:67][C:68]6[C:73]([CH:74]=5)=[CH:72][CH:71]=[CH:70][CH:69]=6)[CH2:63][CH2:64]4)[CH2:15][C:8]=3[CH:7]=[C:6]([Br:26])[C:5]=2[NH:4][N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 673176623-piperidin-4-yl-1H-quinolin-2-one;hydrochlorideHCID 178525536HCID 178525536, compound

Product 1

HCID 178520721HCID 178520721, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-2-(1,4-Dibromo-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid (44 mg, 0.088 mmol) was dissolved in N,N-dimethylformamide (1.5 mL). N,N-Diisopropylethylamine (70 μl, 0.402 mmol) was added to the mixture followed by TBTU (31.5 mg, 0.098 mmol). 3-(Piperidin-4-yl)quinolin-2(1H)-one hydrochloride (25.7 mg, 0.097 mmol) was added to the mixture. Reaction stirred at room temperature for 1.5 hours. Reaction was quenched with 50% acetonitrile-water. Mixture was purified by reverse phase prep HPLC (acetonitrile-water-trifluoroacetic acid). Acetonitrile was removed from the fractions by roto-vap. Remaining aqueous was made basic with aqueous sodium bicarbonate. Material was extracted twice with ethyl acetate and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Title compound was obtained as light tan solid in 51% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.91 (s, 1H) 11.78 (s, 1H) 7.71 (s, 1H) 7.62 (d, J=7.93 Hz, 1H) 7.48 (s, 1H) 7.44 (t, J=7.63 Hz, 1H) 7.28 (d, J=8.24 Hz, 1H)7.15 (t, J=7.48 Hz, 1H) 5.58 (d, J=17.70 Hz, 1H) 5.40 (d, J=17.40 Hz, 1H) 4.55 (d, J=11.90 Hz, 1H) 4.29-4.46 (m, 1H) 4.07-4.23 (m, 2H) 3.91-4.05 (m, 1H) 3.11-3.24 (m, 2H) 2.95-3.09 (m, 2H) 2.82-2.95 (m, 1H) 2.64 (t, J=13.12 Hz, 1H) 2.43 (dd, J=16.48, 4.27 Hz, 1H) 1.89-1.96 (m, 1H) 1.78-1.88 (m, 1H) 1.47-1.64 (m, 1H) 1.30-1.46 (m, 1H). High resolution MS m/e (M+H)+=708.0445.

Workup

  1. customReaction
  2. customReaction
  3. customwas quenched with 50% acetonitrile-water
  4. customMixture was purified by reverse phase prep HPLC (acetonitrile-water-trifluoroacetic acid)
  5. customAcetonitrile was removed from the fractions by roto-vap
  6. extractionMaterial was extracted twice with ethyl acetate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-410dc48728b84d5c96c51df33632aab9
Source dataset
uspto-grants-2008_12
Patent number
US07470679B2

Reaction notes

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