Diisopropylethylamine → HCID 178520722, compound

HRID 2378707Notes

Reaction equation

HRID 2378707 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.[F:59][C:60]1[CH:61]=[CH:62][CH:63]=[C:64]2[C:69]=1[NH:68][C:67](=[O:70])[C:66]([CH:71]1[CH2:76][CH2:75][NH:74][CH2:73][CH2:72]1)=[CH:65]2>CN(C)C=O>[Br:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][C:22]([F:24])([F:23])[F:25])[C:13](=[O:20])[C@H:14]([CH2:16][C:17]([N:74]4[CH2:75][CH2:76][CH:71]([C:66]5[C:67](=[O:70])[NH:68][C:69]6[C:64]([CH:65]=5)=[CH:63][CH:62]=[CH:61][C:60]=6[F:59])[CH2:72][CH2:73]4)=[O:18])[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 673189488-Fluoro-3-(piperidin-4-yl)quinolin-2(1H)-one hydrochlorideHCID 178525536HCID 178525536, compound

Product 1

HCID 178520722HCID 178520722, compoundYield 59%

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 (49 mg, 0.098 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 (34.5 mg, 0.107 mmol). 8-Fluoro-3-(piperidin-4-yl)quinolin-2(1H)-one hydrochloride (33.0 mg, 0.117 mmol) was added to the mixture. Reaction stirred at room temperature for 3.5 hours. Reaction was quenched with 50% acetonitrile-water. Material 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 white solid in 59% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.91 (s, 1H) 11.81 (s, 1H) 7.77 (s, 1H) 7.48 (s, 2H) 7.26-7.41 (m, 1H) 7.06-7.18 (m, 1H) 5.58 (d, J=16.79 Hz, 1H) 5.40 (d, J=17.09 Hz, 1H) 4.55 (d, J=12.51 Hz, 1H) 4.28-4.44 (m, 1H) 4.06-4.22 (m, 2H) 3.86-4.07 (m, 1H) 3.13-3.24 (m, 2H) 3.06 (t, J=10.83 Hz, 1H) 2.98 (dd, J=16.48, 8.24 Hz, 1H) 2.84-2.95 (m, 1H) 2.65 (t, J=12.05 Hz, 1H) 2.33-2.48 (m, 1H) 1.93 (d, J=10.07 Hz, 1H) 1.78-1.89 (m, 1H) 1.47-1.62 (m, 1H) 1.32-1.46 (m, 1H). High resolution MS m/e (M+H)+=726.0337.

Workup

  1. customReaction
  2. customReaction
  3. customwas quenched with 50% acetonitrile-water
  4. customMaterial 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-a628a99e29554adeb1e915dd413c5f1a
Source dataset
uspto-grants-2008_12
Patent number
US07470679B2

Reaction notes

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