Diisopropylethylamine → HCID 178520729, compound

HRID 2378992Notes

Reaction equation

HRID 2378992 reaction equation
[Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)[C:13](=[O:20])[C@H:14]([CH2:16][C:17]([OH:19])=O)[CH2:15][C:8]=3[CH:7]=[C:6]([Cl:29])[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:63]1[CH2:68][CH2:67][CH:66]([N:69]2[C:77]3[C:72](=[N:73][CH:74]=[CH:75][CH:76]=3)[NH:71][C:70]2=[O:78])[CH2:65][CH2:64]1>CN(C)C=O>[Cl:1][C:2]1[C:10]2[C:9]3[CH2:11][N:12]([CH2:21][CH2:22][N:23]4[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)[C:13](=[O:20])[C@H:14]([CH2:16][C:17](=[O:19])[N:63]4[CH2:64][CH2:65][CH:66]([N:69]5[C:77]6[C:72](=[N:73][CH:74]=[CH:75][CH:76]=6)[NH:71][C:70]5=[O:78])[CH2:67][CH2:68]4)[CH2:15][C:8]=3[CH:7]=[C:6]([Cl:29])[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 178525539HCID 178525539, compound

Product 1

HCID 178520729HCID 178520729, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-2-(1,4-dichloro-8-oxo-9-(2-(piperidin-1-yl)ethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl)acetic acid (74 mg, 0.168 mmol) was dissolved in N,N-dimethylformamide (2.0 ml). N,N-Diisopropylethylamine (120 μl, 0.689 mmol) was added to the mixture followed successively by TBTU (58 mg, 0.181 mmol) and 1-(piperidin-4-yl)-1H-imidazo[4,5-b]pyridin-2(3H)-one dihydrochloride (58 mg, 0.199 mmol). Reaction stirred at room temperature for 5 hours. Reaction was quenched with 50% acetonitrile-water. Material was purified by reverse phase 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 71% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.86 (s, 1H) 11.55 (s, 1H) 7.90 (s, 1H) 7.84 (d, J=7.63 Hz, 0.6H) 7.59 (d, J=8.24 Hz, 0.4H) 7.33 (s, 1H) 6.84-7.06 (m, 1 H) 5.22-5.36 (m, 2H) 4.40-4.64 (m, 2H) 4.16 (t, J=14.65 Hz, 1H) 3.80-4.02 (m, 2H) 3.12-3.29(m,3H) 2.95-3.09(m, 1H) 2.84-2.96(m, 1H) 2.62-2.78(m, 1 H) 2.53-2.60 (m, 1H) 2.39-2.49 (m, 1H) 2.01-2.33 (m, 5H) 1.62-1.98 (m, 4H) 1.09-1.22 (m, 6H). High resolution MS m/e (M+H)+=639.2393.

Workup

  1. customReaction
  2. customReaction
  3. customwas quenched with 50% acetonitrile-water
  4. customMaterial was purified by reverse phase 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-bc0bb7eee5104abeb3c50b17a2de615c
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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