Diisopropylethylamine → HCID 178520724, compound

HRID 2378987Notes

Reaction equation

HRID 2378987 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.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>[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: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]([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 222931811-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochlorideHCID 178525536HCID 178525536, compound

Product 1

HCID 178520724HCID 178520724, compoundYield 34%

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 (51 mg, 0.102 mmol) was dissolved in N,N-dimethylformamide (1.5 mL). N,N-Diisopropylethylamine (90 μl, 0.517 mmol) was added to the mixture followed by TBTU (36.1 mg, 0.112 mmol). 1-(Piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one dihydrochloride (36.5 mg, 0.125 mmol) was added to the mixture. Reaction stirred at room temperature for 2.5 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 fraction by roto-vap. Remaining aqueous was made basic with aqueous sodium bicarbonate. Material was extracted twice with ethyl acetate. Organics were dried MgSO4, filtered and then concentrated to dryness. Title compound was obtained as white solid in 34% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.92 (s, 1H) 11.56 (d, J=6.41 Hz, 1H) 7.90 (d, J=5.19 Hz, 1H 7.65 (dd, J=69.89, 7.93 Hz, 1H) 7.49 (s, 1H) 6.81-7.06 (m, 1H) 5.54-5.68 (m, 1H) 5.35-5.50 (m, 1H) 4.49-4.63 (m, 1H) 4.32-4.42 (m, 1H) 4.20-4.49 (m, 1H) 4.13-4.20 (m, 1H) 3.93-4.14 (m, 1H) 3.22 (d, J=16.17 Hz, 2H) 2.97-3.12 (m, 1H) 2.86-2.97 (m, 1H) 2.67-2.79 (m, 1H) 2.52-2.66 (m, 1H) 2.42-2.48 (m, J=17.09 Hz, 1H) 2.34-2.42 (m, 1H) 1.93-2.32 (m, 1H) 1.74-1.85 (m, 1H) 1.65-1.74 (m, 1H). High resolution MS m/e (M+H)+=698.0314.

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 fraction by roto-vap
  6. extractionMaterial was extracted twice with ethyl acetate
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-f8d38a376f804c3fa58be2a4d29cd45a
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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