Triethylamine → HCID 136046863, compound

HRID 1884058Notes

Reaction equation

HRID 1884058 reaction equation
[NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[CH:14][CH:15]=[C:16]([NH:17][C:18]4[CH:26]=[CH:25][C:21]([C:22](O)=[O:23])=[CH:20][CH:19]=4)[C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1.Cl.[CH2:28]([O:30][C:31](=[O:41])[C@H:32]([CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])[NH2:33])[CH3:29].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[NH2:1][C:2]1[NH:11][C:10](=[O:12])[C:9]2[C:8]3[CH:13]=[CH:14][CH:15]=[C:16]([NH:17][C:18]4[CH:26]=[CH:25][C:21]([C:22]([NH:33][C@H:32]([C:31]([O:30][CH2:28][CH3:29])=[O:41])[CH2:34][CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])=[O:23])=[CH:20][CH:19]=4)[C:7]=3[CH:6]=[CH:5][C:4]=2[N:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 135838136HCID 135838136, compound

Product 1

HCID 136046863HCID 136046863, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of N-(7-(4-cyanoanilino)-1,2-dihydro-1-oxobenzo[f]-quinazolin-3-yl)pivalamide (82 mg, 0.20 mmol) in ethanol (1 ml) and 1N NaOH (4 ml) was stirred under nitrogen at reflux overnight. The solution was allowed to cool, acidified to pH 3 with concentrated HCl, the resulting suspension stirred for 30 minutes,then filtered. The solid was washed with water and dried at 120° C. under reduced pressure to give 4-((3-amino-1,2-dihydro-1-oxobenzo[f]quinazolin-7-yl)amino)benzoic acid. 1H NMR (DMSO-d6, 200 MHz) δ: 6.85 (d, J=9 Hz, 2H, Ar), 7.30 (br s, 2H, NH2), 7.39 (d, J=9 Hz, 1H Ar), 7.43 (d, J=8 Hz, 1H, Ar), 7.64 (t, J=8 Hz, 1H, Ar), 7.73 (d, J=9 Hz, 2H, Ar), 8.28 (d, J=9 Hz, 1H, Ar), 8.85 (s, 1H, C7—NH), 9.44 (d, J=9 Hz, 1H, Ar), 11.5-12.9 (2H, CO2H and N2H). A solution of the foregoing benzoic acid, L-glutamic acid diethyl ester hydrochloride (80 mg, 0.33 mmol) (Aldrich), benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate (90 mg, 0.20 mmol) (Richelieu Biotechnologies), and triethylamine (90 l, 0.64 mmol) in DMF (6 ml) was stirred at room temperature for 1 hour, then concentrated under high vacuum. The residue was purified by chromatography on silica gel (10-15 g) three times eluting with methanol/methylene chloride. Water (˜5 ml) was added to a solution of the solid in ethanol, the ethanol removed under vacuum, and the solid filtered, washed with water, and dried under high vacuum to give diethyl N-(4-((3-amino-1,2-dihydro-1-oxobenzo[f]quinazolin-7-yl)amino)benzoyl)-L-glutamate (35 mg). 1H NMR (DMSO-d6, 200 MHz) δ: 1.14 (t, J=7 Hz, 3H, CH3), 1.16 (t, J=7 Hz, 3H, CH3), 1.85-2.15 (m, 2H, gluCH2), 2.40 (t, J=7 Hz, 2H, gluCH2), 4.03 (q, J=7 Hz, 2H, esterCH2), 4.08 (q, J=7 Hz, 2H, esterCH2), 4.30-4.45 (m, 1H, gluCH), 6.63 (br s, 2H, NH2), 6.85 (d, J=9 Hz, 2H, Ar), 7.29 (d, J=9 Hz, 1H, Ar), 7.35 (d, J=8 Hz, 1H, Ar), 7.56 (t, J=8 Hz, 1H, Ar), 7.71 (d, J=9 Hz, 2H, Ar), 8.18 (d, J=9 Hz, 1H, Ar), 8.36 (d, J=7 Hz, 1H, gluNH), 8.64 (s, 1H, C7—NH), 9.45 (d, J=9 Hz, 1H, Ar), 11.22 (br s, 1H, N2H). Mass spectrum (CI-CH4): 532 (M+1, 62.5%), Anal. Calculated for C28H29N5O6.H2O: C, 61.19; H, 5.69; N, 12.74. Found: C, 61.20; H, 5.44; N, 12.68.

Workup

  1. concentrationconcentrated under high vacuum
  2. customThe residue was purified by chromatography on silica gel (10-15 g) three times
  3. washeluting with methanol/methylene chloride
  4. additionWater (˜5 ml) was added to a solution of the solid in ethanol
  5. customthe ethanol removed under vacuum
  6. filtrationthe solid filtered
  7. washwashed with water
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-70ecb2e606ae46cb837338359cbb2e4f
Source dataset
uspto-grants-2004_07
Patent number
US06762188B1

Reaction notes

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