Hydrochloric Acid → HCID 86753597, compound

HRID 343188Notes

Reaction equation

HRID 343188 reaction equation
[CH:1]([C:4]([C:31]1[CH:36]=[CH:35]C=CC=1)(C(=O)N)[N:5]1[C:11](=[O:12])[CH:10](CC(O)=O)[C:9](=[O:17])[N:8](C2C=CC=CC=2)[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]1=2)(C)[CH3:2].N[C:38]1[CH:39]=[C:40]([CH:46]=[CH:47][CH:48]=1)[C:41]([O:43][CH2:44][CH3:45])=[O:42].F[P-](F)(F)(F)(F)F.[N:56]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:60]2[CH:61]=[CH:62][CH:63]=[CH:64][C:59]=2N=N1.C1C=C[C:79]2N(O)N=N[C:80]=2[CH:81]=1.Cl>CN(C=O)C.CN(C1C=CN=CC=1)C>[O:17]=[C:9]1[N:8]([CH2:10][C:11]([N:56]([CH:80]([CH3:79])[CH3:81])[C:60]2[CH:59]=[CH:64][CH:63]=[CH:62][CH:61]=2)=[O:12])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:4]2[CH:31]=[CH:36][CH:35]=[CH:2][CH:1]=2)[C:11](=[O:12])[C:10]1([C:9](=[O:17])[NH2:8])[C:38]1[CH:48]=[CH:47][CH:46]=[C:40]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH:39]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11400Ethyl 3-aminobenzoateHCID 757711-HydroxybenzotriazoleHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 67697792HCID 67697792, compound

Product 1

HCID 86753597HCID 86753597, compoundYield 149.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.26 g (0.54 mmol) of [1-(isopropyl-phenyl-carbamoylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]acetic acid, prepared as in Intermediate 32, and 0.08 mL (0.54 mmol) of ethyl 3-aminobenzoate in 2 mL of DMF is added 0.23 g (0.54 mmol) of BOP, 72 mg (0.54 mmol) of HOBT and 63 mg (0.54 mmol) of DMAP. The black solution is stirred at RT for 21 h and subsequently poured into 20 mL of 1N HCl. The mixture is extracted with ethyl acetate (×3), washed with 1N HCl and brine, dried over MgSO4 and concentrated in vacuo. The resulting yellow oil is purified by silica gel flash chromatography (40% ethyl acetate/petroleum ether) followed by recrystallization from ethyl acetate/petroleum ether to give 0.25 g of the title compound as a white powder: mp. 187°-8° C.; 1H NMR (CDCl3, 300 MHz) δ8.01 (d, 1H, J=22), 7.77 (t, 1H, J=8), 7.5-7.2 (m, 15H), 7.12 (t, 1H, J=8), 6.94 (d, 1H, J=8), 5.02 (m, 1H), 4.36 (q, 2H, J=7), 4.26 (q, 2H, J=17), 4.04 (t, 1H, J=7), 3.10 (m, 1H), 1.39 (t, 3H, J=7), 1.08 (dd, 6H, J=4,7); low resolution MS (FAB) m/e 633 (MH+); Anal. (C37H36N4O6.0.25H2O) Calcd C, 69.7; H, 5.8; N, 8.8; Found: C, 69.6; H, 5.7; N, 8.8.

Workup

  1. extractionThe mixture is extracted with ethyl acetate (×3)
  2. washwashed with 1N HCl and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting yellow oil is purified by silica gel flash chromatography (40% ethyl acetate/petroleum ether)
  6. customfollowed by recrystallization from ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-1c271719eed0439781d466685723e46d
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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