Diisopropylethylamine → HCID 178473829, compound

HRID 874460Notes

Reaction equation

HRID 874460 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[C:21]3=[C:22]4[C:16](=[C:17]5[N:26]([CH3:27])[CH:25]=[CH:24][C:23]([NH2:28])=[C:18]5[CH:19]=[CH:20]3)[C:15](=[O:29])[NH:14][C:13]4=[CH:12][CH2:11]2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:30][C:31]1[S:32][C:33]([CH2:36][C:37](O)=[O:38])=[CH:34][N:35]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C>CN(C)C(=O)C>[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[C:21]3=[C:22]4[C:16](=[C:17]5[N:26]([CH3:27])[CH:25]=[CH:24][C:23]([NH:28][C:37](=[O:38])[CH2:36][C:33]6[S:32][C:31]([CH3:30])=[N:35][CH:34]=6)=[C:18]5[CH:19]=[CH:20]3)[C:15](=[O:29])[NH:14][C:13]4=[CH:12][CH2:11]2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6852046(2-Methyl-1,3-thiazol-5-yl)acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178473828HCID 178473828, compound

Product 1

HCID 178473829HCID 178473829, compoundYield 95.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

A mixture of Example 73d (0.02 g, 0.051 mmol), 2-(2-methylthiazol-5-yl)acetic acid (0.012 g, 0.077 mmol), and 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.029 g, 0.077 mmol) in N,N-dimethyl acetamide (0.5 mL) was treated with N-ethyl-N-isopropylpropan-2-amine (0.027 mL, 0.153 mmol) and stirred at ambient temperature for 22 hours. The reaction mixture was partitioned between ethyl acetate and water and washed with saturated aqueous sodium chloride. The aqueous layers were combined, saturated with solid sodium chloride and extracted with ethyl acetate (4×100 mL). The organic layers were combined, dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography (silica gel, 0-15% methanol in dichloromethane). The material was further purified by reverse phase HPLC(C18, acetonitrile/water (0.1% TFA), 10-100%) to provide 0.0258 g (78%) of the title compound as the TFA salt. 1H NMR (400 MHz, PYRIDINE-d5) δ 11.24 (s, 1H), 10.34 (s, 1H), 8.34 (d, J=2.44 Hz, 1H), 7.62 (s, 1H), 7.54 (d, J=2.75 Hz, 1H), 7.35 (s, 1H), 7.21 (d, J=8.54 Hz, 1H), 6.89 (s, 1H), 4.20 (s, 2H), 4.13 (s, 3H), 4.07 (s, 2H), 3.64 (m, 1H), 3.25 (m, 1H), 2.63 (m, 2H), 2.55 (s, 3H), 2.59 (m, 1H), 1.93 (s, 3H), 1.69 (m, 2H), 1.50 (m, 2H). MS (ESI+) m/z 531.1 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washwashed with saturated aqueous sodium chloride
  3. extractionextracted with ethyl acetate (4×100 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (silica gel, 0-15% methanol in dichloromethane)
  8. customThe material was further purified by reverse phase HPLC(C18, acetonitrile/water (0.1% TFA), 10-100%)

Sources & evidence

ORD record
ord-40e7212eed974b25b552b16da2c5e65e
Source dataset
uspto-grants-2015_03
Patent number
US08980879B2

Reaction notes

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