Diisopropylethylamine → HCID 178497578, compound

HRID 1945356Notes

Reaction equation

HRID 1945356 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)C=O.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 dimethylformamide (50 mL). The reaction mixture was stirred 3 h and solvent removed in vacuo, and the residue was diluted with ethyl acetate, washed with 0.1N HCl, sat'd NaHCO3, brine, and dried (Na2SO4). 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 ethyl acetate, washed with sat'd NaHCO3 soln., brine, and dried (Na2SO4). Concentration gave a residue that was divided into two lots, and each lot pre-adsorbed onto SiO2 (dichloromethane), applied to a 40 M Biotage SiO2 column, and eluted by gradient 10%-100% B (1440 mL); A=hexanes; B=ethyl acetate to give J.33 (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 (Cond.-D2): 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 ethyl acetate
  3. washwashed with 0.1N HCl
  4. dry with materialdried (Na2SO4)
  5. concentrationConcentration
  6. customgave a reddish brown viscous oil which
  7. customThe solvent was removed in vacuo
  8. additionthe residue was diluted with ethyl acetate
  9. washwashed with sat'd NaHCO3 soln
  10. dry with material, brine, and dried (Na2SO4)
  11. concentrationConcentration
  12. customgave a residue that
  13. washeluted by gradient 10%-100% B (1440 mL)

Sources & evidence

ORD record
ord-af7c2fd58d4344aabd8387804547f57b
Source dataset
uspto-grants-2013_03
Patent number
US08394968B2

Reaction notes

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