Hydrochloric Acid → HCID 86751436, compound

HRID 1490110Notes

Reaction equation

HRID 1490110 reaction equation
[NH2:1][CH:2]1[N:8]=[C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[N:4]([CH2:20][CH2:21][CH3:22])[C:3]1=[O:23].C([NH:31][C@@H:32]([C:40](O)=[O:41])[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)(OC(C)(C)C)=O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(=O)([O-])O.[Na+].Cl.P(=O)(O)(O)O>CN(C)C=O.ClCCl.CO.N.O.C(N(CC)CC)C.C(#N)C.C(OCC)(=O)C>[NH2:31][CH:32]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:40]([NH:1][CH:2]1[N:8]=[C:7]([N:9]2[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH2:14]2)[C:6]2[CH:16]=[CH:17][CH:18]=[CH:19][C:5]=2[N:4]([CH2:20][CH2:21][CH3:22])[C:3]1=[O:23])=[O:41]

Participants

14

Reactant 7

HCID 313Hydrochloric AcidHCID 1004Phosphoric AcidHCID 757711-HydroxybenzotriazoleHCID 516892Sodium Bicarbonate2×HCID 637610Boc-D-phenylalanineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15288176HCID 15288176, compound

Product 1

HCID 86751436HCID 86751436, compound

Reagents, catalysts & solvents 6

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolventHCID 21584172Ammonia methanol dichloromethaneSolvent

Procedure

To a stirred solution of 3-amino-1,2-dihydro-5-(4-methylpiperazin-1-yl)-1-propyl-3H-1,4-benzodiazepin-2-one (2.96 g) in anhydrous dimethylformamide (30 ml) was added BOC-D-phenylalanine (2.61 g), 1-hydroxybenzotriazole (1.33 g), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (1.89 g) and triethylamine (1.37 ml). After stirring at room temperature for 15 minutes the solution was treated with saturated sodium hydrogen carbonate solution then extracted with ethyl acetate (4×100 ml). The combined organic phases were washed with saturated sodium chloride solution, dried (Na2SO4), evaporated to dryness and the residue purified by column chromatography on silica using 5% methanol/dichloromethane to 10% methanol/dichloromethane. The product obtained (5.28 g) was treated at 0° C. with ethyl acetate (100 ml) saturated with hydrogen chloride gas and stirred at 0° C. for 1 hour. The solution was basified to pH 9 with saturated sodium hydrogen carbonate solution, the organic layer was separated and the aqueous re-extracted with ethyl acetate (4×100 ml). The combined organic phases were dried (Na2SO4) and the more polar (by silica tlc) diastereomer crystallised from methanol/diethyl ether to afford a solid (460 mg. mp 152°-153° C.; Rf 0.50 in dichloromethane/methanol/ammonia (9:1:0.1) on silica plates. HPLC (Spherisorb ODS2 column, 25% acetonitrile/75% of 0.2% triethylamine in water, pH to 3 with orthophosphoric acid): Rt 5.09 minutes, 99.5% pure. δH (360 MHz, DMSO-d6) δ0.68 (3H, t, J=7 Hz), 1.20-1.29 (1H, m), 1.37-1.44 (1H, m), 2.19 (3H, s), 2.25-2.35 (2H, m), 2.40-2,48 (2H, m), 2.59 (1H, dd, J=9 and 13 Hz), 3.00 (1H, dd, J=4 and 13 Hz), 3.10-3.30 (4H, m), 3.47 (1H, dd, J=4 and 9 Hz), 3.60-3.68 (1H, m), 4.19-4.28 (1H, m), 4.97 (1H, d, J=8 Hz), 7.16-7.30 (5H, m), 7.36-7.42 (1H, m), 7.55 (1H, d, J=8 Hz), 7.63-7.66 (2H, m), 8.76 (1H, d, J=8 Hz). (Found: C, 67.62; H, 7.24; N, 18.17. C26H34N6O2 requires 67.51; H, 7.41; N, 18.17%).

Workup

  1. extractionthen extracted with ethyl acetate (4×100 ml)
  2. washThe combined organic phases were washed with saturated sodium chloride solution
  3. dry with materialdried (Na2SO4)
  4. customevaporated to dryness
  5. customthe residue purified by column chromatography on silica using 5% methanol/dichloromethane to 10% methanol/dichloromethane
  6. customThe product obtained (5.28 g)
  7. stirringstirred at 0° C. for 1 hour
  8. customthe organic layer was separated
  9. extractionthe aqueous re-extracted with ethyl acetate (4×100 ml)
  10. dry with materialThe combined organic phases were dried (Na2SO4)
  11. customthe more polar (by silica tlc) diastereomer crystallised from methanol/diethyl ether
  12. customto afford a solid (460 mg

Sources & evidence

ORD record
ord-4d863bae8f2a4ddbb49ad3343e178a9f
Source dataset
uspto-grants-1997_10
Patent number
US05681833

Reaction notes

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