Diisopropylethylamine → HCID 178497578, compound

HRID 603296Notes

Reaction equation

HRID 603296 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C:26]1[C:35]([NH2:36])=[CH:34][CH:33]=[CH:32][C:27]=1[C:28]([O:30][CH3:31])=[O:29].[C:37]([N:44]1[CH2:51][CH2:50][CH2:49][C@H:45]1[C:46](O)=O)([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38].CCN(C(C)C)C(C)C>CN(C=O)C.C(O)(=O)C>[C:40]([O:39][C:37]([N:44]1[CH2:51][CH2:50][CH2:49][C@H:45]1[C:46]1[NH:25][C:26]2[C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:32][CH:33]=[CH:34][C:35]=2[N:36]=1)=[O:38])([CH3:43])([CH3:41])[CH3:42]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 5718252,3-Diaminobenzoic acid methyl esterHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 178497578HCID 178497578, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

HATU (10.66 g, 28.0 mmol) was added in one portion to a stirred solution of methyl 2,3-diaminobenzoate (4.1 g, 24.7 mmol), N-Boc-L-proline (5.49 g, 25.5 mmol), and Hunig's base (4.9 mL, 28.0 mmol) in DMF (50 mL). The reaction mixture was stirred 3 h and solvent removed in vacuo, and the residue was diluted with EtOAc, washed with 0.1N HCl, sat'd NaHCO3, brine, dried (Na2SO4), and filtered. Concentration gave a reddish brown viscous oil which was taken up in glacial acetic acid (60 mL) and heated at 60° C. for 16 h. The solvent was removed in vacuo, and the residue was diluted with EtOAc, washed with sat'd NaHCO3 soln, brine, dried (Na2SO4), and filtered. Concentration gave a residue that was divided into two lots, and each lot was pre-adsorbed onto SiO2 (CH2Cl2), applied to a 40 M Biotage SiO2 column, and eluted by gradient 10%-100% B (1440 mL); A=Hex; B=EtOAc to give J1, (S)-methyl 2-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-1H-benzo[d]imidazole-7-carboxylate (7.05 g, 83%) as a reddish oil. 1H NMR (500 MHz, DMSO-d6) δ: 7.86 (d, J=7.9 Hz, 1H), 7.78 (t, J=5 Hz, 1H), 7.28-7.24 (m, 1H), 5.20-5.11 (m, 1H), 3.95 (s, 3H), 3.60-3.52 (m, 1H), 3.43-3.38 (m, 1H), 2.33-2.22 (m, 1H), 2.15-2.0 (m, 2H), 1.91-1.86 (m, 1H), 1.40/1.05 (s, 9H). LC (D-Cond. 2): RT=1.86 min; LC/MS Anal. Calcd. for [M+H]+ C18H24N3O4: 346.18. found 346.26. HRMS: Anal. Calcd. for [M+H]+ C18H24N3O4: 346.1767. found: 346.1776.

Workup

  1. customsolvent removed in vacuo
  2. additionthe residue was diluted with EtOAc
  3. washwashed with 0.1N HCl
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationConcentration
  7. customgave a reddish brown viscous oil which
  8. customThe solvent was removed in vacuo
  9. additionthe residue was diluted with EtOAc
  10. washwashed with sat'd NaHCO3 soln
  11. dry with materialbrine, dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationConcentration
  14. customgave a residue that
  15. washeluted by gradient 10%-100% B (1440 mL)

Sources & evidence

ORD record
ord-311431d80f0148389eb2fd41a85e04b4
Source dataset
uspto-grants-2011_03
Patent number
US07906655B2

Reaction notes

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