Diisopropylethylamine → HCID 68485337, compound

HRID 1875089Notes

Reaction equation

HRID 1875089 reaction equation
CCN(C(C)C)C(C)C.[NH2:10][CH2:11][C:12]1[C:13]([F:29])=[C:14]([O:19][C:20]2[CH:21]=[C:22]([CH:25]=[C:26]([Cl:28])[CH:27]=2)[C:23]#[N:24])[C:15]([Cl:18])=[CH:16][CH:17]=1.[CH3:30][C:31]1[NH:35][C:34](=[O:36])[NH:33][C:32]=1[C:37](O)=[O:38].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(=O)(O)[O-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][NH:10][C:37]([C:32]2[NH:33][C:34](=[O:36])[NH:35][C:31]=2[CH3:30])=[O:38])=[C:13]([F:29])[C:14]=1[O:19][C:20]1[CH:21]=[C:22]([C:23]#[N:24])[CH:25]=[C:26]([Cl:28])[CH:27]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 135585675-Methyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxylic acidHCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 68485337HCID 68485337, compoundYield 95.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DIPEA (0.20 mL, 1.16 mmol) was added to a mixture of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.15 g, 0.48 mmol), 5-methyl-2-oxo-2,3-dihydro-1H-imidazole-4-carboxylic acid (0.080 g, 0.58 mmol) and HATU (0.24 g, 0.63 mmol) in DMF (3 mL). The yellow solution was stirred at RT under nitrogen for 24 h then ethyl acetate (50 mL) and saturated sodium bicarbonate solution (100 mL) was added. The organic layer was separated, washed with saturated sodium bicarbonate solution (50 mL), water (50 mL), brine (50 mL) and dried over MgSO4. The mixture was filtered and the solvent was removed under vacuum. The crude material was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA) to give the title compound (0.20 g, 10%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.42 (br. s., 1H), 9.75 (br. s., 1H), 7.74-7.95 (m, 2H), 7.42-7.57 (m, 3H), 7.37 (t, 1H), 4.44 (d, 2H), 2.20 (s, 3H). LCMS m/z 437.0 (M+H).

Workup

  1. customThe organic layer was separated
  2. washwashed with saturated sodium bicarbonate solution (50 mL), water (50 mL), brine (50 mL)
  3. dry with materialdried over MgSO4
  4. filtrationThe mixture was filtered
  5. customthe solvent was removed under vacuum
  6. customThe crude material was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA)

Sources & evidence

ORD record
ord-cb378c72989e4821a19e2ab29970c94c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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