Diisopropylethylamine → HCID 71285571, compound

HRID 1182690Notes

Reaction equation

HRID 1182690 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([CH3:14])=[N:10]2)=[C:5]2[NH:15][CH:16]=[C:17]([C:18](=[O:22])[C:19]([OH:21])=O)[C:4]=12.[C:23]1([N:29]2[C:33]([N:34]3[CH2:37][C:36]4([CH2:40][NH:39][CH2:38]4)[CH2:35]3)=[N:32][N:31]=[N:30]2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[N:7][C:6]([N:9]2[CH:13]=[N:12][C:11]([CH3:14])=[N:10]2)=[C:5]2[NH:15][CH:16]=[C:17]([C:18](=[O:22])[C:19]([N:39]3[CH2:40][C:36]4([CH2:37][N:34]([C:33]5[N:29]([C:23]6[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=6)[N:30]=[N:31][N:32]=5)[CH2:35]4)[CH2:38]3)=[O:21])[C:4]=12

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 596815922-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acidHCID 71285281HCID 71285281, compound

Product 1

HCID 71285571HCID 71285571, compoundYield 34.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoacetic acid (0.050 g), 2-(1-phenyl-1H-tetrazol-5-yl)-2,6-diazaspiro[3.3]heptane (0.044 g), BOP reagent (0.080 g) and Hunig's base (0.2 mL) were mixed in dry DMF (2 mL). The reaction mixture was stirred at room temperature for 16 hours. The mixture was quenched with methanol (10 mL) and volatiles were removed under reduced pressure. The resulting oil was diluted with ethyl acetate (50 mL), washed with 10% NaHCO3 (10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting crude was purified by silica gel column chromatography using MeOH/CHCl3 (1:9) as an eluent to afford 1-(4-methoxy-7-(3-methyl-1H-1,2,4-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(6-(1-phenyl-1H-tetrazol-5-yl)-2,6-diazaspiro[3.3]heptan-2-yl)ethane-1,2-dione (30 mg). 1H NMR (400 MHz, DMSO-d6): δ ppm 2.47-2.49 (s, 3H), 3.93 (s, 4H), 4.08-4.13 (m, 2H), 4.20-4.36 (d, 2H), 7.54-7.62 (m, 5H), 7.84 (s, 1H), 8.30-8.32 (s, 1H), 9.22 (s, 1H), 12.26 (bs, 1H). LCMS MS (M+H)+ Calcd.: 526, Observ.: 526.

Workup

  1. customThe mixture was quenched with methanol (10 mL) and volatiles
  2. customwere removed under reduced pressure
  3. additionThe resulting oil was diluted with ethyl acetate (50 mL)
  4. washwashed with 10% NaHCO3 (10 mL) and brine (10 mL)
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting crude was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5d3525e1d1f34ae3939160f2002a5635
Source dataset
uspto-grants-2014_03
Patent number
US08664213B2

Reaction notes

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