Diisopropylethylamine → HCID 11853712, compound

HRID 1446769Notes

Reaction equation

HRID 1446769 reaction equation
Cl.Cl.[F:3][C:4]1[CH:9]=[C:8]([C:10]2[N:14]3[CH:15]=[CH:16][C:17](C4C=CC=CN=4)=[CH:18][C:13]3=[N:12][CH:11]=2)[CH:7]=[CH:6][C:5]=1[CH2:25][C:26](O)=[O:27].[C:29]([C:33]1[S:37][C:36]([NH2:38])=[N:35][C:34]=1[CH2:39][N:40]1[CH2:45][CH2:44][O:43][CH2:42][CH2:41]1)([CH3:32])([CH3:31])[CH3:30].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)[C:66]2[N:67]=[CH:68][CH:69]=[CH:70][C:65]=2N=N1>CN(C=O)C>[F:3][C:4]1[CH:9]=[C:8]([C:10]2[N:14]3[CH:15]=[CH:16][C:17]([C:70]4[CH:69]=[CH:68][N:67]=[CH:66][CH:65]=4)=[CH:18][C:13]3=[N:12][CH:11]=2)[CH:7]=[CH:6][C:5]=1[CH2:25][C:26]([NH:38][C:36]1[S:37][C:33]([C:29]([CH3:32])([CH3:30])[CH3:31])=[C:34]([CH2:39][N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[N:35]=1)=[O:27]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86634313HCID 86634313, compoundHCID 131727907HCID 131727907, compound

Product 1

HCID 11853712HCID 11853712, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Combine [2-fluoro-4-(7-pyridin-2-yl-imidazo[1,2-a]pyridin-3-yl)-phenyl]-acetic acid, dihydrochloride (0.500 g, 1.19 mmol) and 5-tert-Butyl-4-morpholin-4-ylmethyl-thiazol-2-ylamine (0.334 g, 1.31 mmol) in DMF (6 mL). Add N,N-diisopropyl-ethylamine (0.54 mL, 3.93 mmol), then O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetra-methyluronium hexafluorophosphate (0.498 g, 1.31 mmol). The reaction mixture is stirred over the weekend under N2. Purify using an SCX cartridge (10 g VARIAN BondElut®), eluting with 1:1 methanol:dichloromethane, then 1:1 2 M NH3 in methanol:dichloromethane. Concentrate the latter and purify via reverse phase chromatography using a 25 cm by 50.8 mm (i.d.) column w/10 micron particles (MeCN/0.03% HCl H2O (5:95) to 100% MeCN; 30 min). Partition between ethyl acetate and 1 N NaOH. Dry the organic layer over magnesium sulfate, filter, and concentrate to the title compound (0.190 g, 27%). MS(ES), m/z 585 (M+1).

Workup

  1. customPurify
  2. washeluting with 1:1 methanol
  3. concentrationConcentrate the latter
  4. custompurify via reverse phase chromatography
  5. customby 50.8 mm (i.d.) column w/10 micron particles (MeCN/0.03% HCl H2O (5:95) to 100% MeCN; 30 min)
  6. customPartition between ethyl acetate and 1 N NaOH
  7. dry with materialDry the organic layer over magnesium sulfate
  8. filtrationfilter
  9. concentrationconcentrate to the title compound (0.190 g, 27%)

Sources & evidence

ORD record
ord-459a1aa853384c38aabe99e6eff4585d
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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