Diisopropylethylamine → HCID 178520727, compound

HRID 2378990Notes

Reaction equation

HRID 2378990 reaction equation
[Cl: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]([Cl: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.Cl.[NH:60]1[CH2:65][CH2:64][CH:63]([N:66]2[C:74]3[C:69](=[N:70][CH:71]=[CH:72][CH:73]=3)[NH:68][C:67]2=[O:75])[CH2:62][CH2:61]1>CN(C)C=O>[Cl: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:60]4[CH2:61][CH2:62][CH:63]([N:66]5[C:74]6[C:69](=[N:70][CH:71]=[CH:72][CH:73]=6)[NH:68][C:67]5=[O:75])[CH2:64][CH2:65]4)[CH2:15][C:8]=3[CH:7]=[C:6]([Cl: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 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 178525538HCID 178525538, compound

Product 1

HCID 178520727HCID 178520727, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-2-(1,4-Dichloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid (110 mg, 0.268 mmol) was dissolved in N,N-dimethylformamide (2.0 ml). N,N-Diisopropylethylamine (150 μl, 0.861 mmol) was added to the mixture followed successively by TBTU (92 mg, 0.287 mmol) and 1-(piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one dihydrochloride (92 mg, 0.316 mmol). Reaction stirred at room temperature for 5 hours. Reaction was quenched with 50% acetonitrile-water. Material was purified by prep HPLC (water-acetonitrile-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 70% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.89 (s, 1H) 11.55 (s, 1H) 7.90 (dd, J=5.19, 1.22 Hz, 1 H) 7.64 (dd, J=70.19, 7.93 Hz, 1H) 7.35 (s, 1H) 6.99 (dd, J=7.78, 5.34 Hz, 0.4H) 6.90 (dd, J=7.93, 5.19 Hz, 0.6H) 5.44 (d, J=4.88 Hz, 2H) 4.35-4.62 (m, 3H) 3.95-4.32 (m, 3H) 3.15-3.28 (m, 2H) 2.85-3.12 (m, 2H) 2.61-2.76 (m, 1H) 2.20-2.47 (m, 2H) 1.93-2.12 (m, 1H) 1.64-1.87 (m, 2H). High resolution MS m/e (M+H)+=610.1328.

Workup

  1. customReaction
  2. customReaction
  3. customwas quenched with 50% acetonitrile-water
  4. customMaterial was purified by prep HPLC (water-acetonitrile-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-5ce105863cf34d00ad46bdefeb6a9148
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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