Diisopropylethylamine → HCID 178520728, compound

HRID 2378991Notes

Reaction equation

HRID 2378991 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.[NH:61]1[CH2:66][CH2:65][CH:64]([N:67]2[CH2:73][CH2:72][C:71]3[CH:74]=[CH:75][CH:76]=[CH:77][C:70]=3[NH:69][C:68]2=[O:78])[CH2:63][CH2:62]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[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]4)[C:13](=[O:20])[C@H:14]([CH2:16][C:17](=[O:19])[N:61]4[CH2:62][CH2:63][CH:64]([N:67]5[CH2:73][CH2:72][C:71]6[CH:74]=[CH:75][CH:76]=[CH:77][C:70]=6[NH:69][C:68]5=[O:78])[CH2:65][CH2:66]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 113795873-(Piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-oneHCID 178525539HCID 178525539, compound

Product 1

HCID 178520728HCID 178520728, compoundYield 54%

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 (54 mg, 0.123 mmol) was dissolved in N,N-dimethylformamide (1.5 ml). N,N-Diisopropylethylamine (100 μL, 0.574 mmol) was added to the mixture followed successively by TBTU (42 mg, 0.131 mmol) and then 3-(piperidin-4-yl)-4,5-dihydro-1H-benzo[d][1,3]diazepin-2(3H)-one (43 mg, 0.175 mmol). Reaction stirred at room temperature for 4 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 54% yield. 1H NMR (500 MHz, DMSO-D6) δ ppm 13.85 (s, 1H) 8.50 (s, 1H) 7.32 (s, 1H) 6.96-7.11 (m, 3H) 6.80 (s, 1H) 5.26 (s, 2H) 4.44-4.54 (m, 1H) 4.27-4.37 (m, 1H) 4.06 (d, J=14.04 Hz, 1H) 3.79-3.96 (m, 2H) 3.34-3.44 (m, 2H) 3.05-3.25 (m, 3H) 2.82-3.02 (m, 4H) 2.45-2.66 (m, 2H) 2.28-2.40 (m, 1H) 2.04-2.26 (m, 4H) 1.80-1.95 (m, 2H) 1.58-1.73 (m, 2H) 1.40-1.57 (m, 1H) 1.18 (bs, 6H). High resolution MS m/e (M+H)+=666.2756.

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-b9fe8534a6f5406d962b0276f64803d0
Source dataset
uspto-grants-2008_12
Patent number
US07470680B2

Reaction notes

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