Diisopropylethylamine → HCID 57863464, compound

HRID 1446768Notes

Reaction equation

HRID 1446768 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]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=4)=[CH:18][C:13]3=[N:12][CH:11]=2)[CH:7]=[CH:6][C:5]=1[CH2:25][C:26]([OH:28])=O.[CH3:29][N:30]([CH2:32][C:33]1[N:34]=[C:35]([NH2:42])[S:36][C:37]=1[C:38]1([CH3:41])[CH2:40][CH2:39]1)[CH3:31].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>CN(C=O)C>[CH3:31][N:30]([CH2:32][C:33]1[N:34]=[C:35]([NH:42][C:26](=[O:28])[CH2:25][C:5]2[CH:6]=[CH:7][C:8]([C:10]3[N:14]4[CH:15]=[CH:16][C:17]([C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=5)=[CH:18][C:13]4=[N:12][CH:11]=3)=[CH:9][C:4]=2[F:3])[S:36][C:37]=1[C:38]1([CH3:41])[CH2:40][CH2:39]1)[CH3:29]

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 86634312HCID 86634312, compoundHCID 131727907HCID 131727907, compound

Product 1

HCID 57863464HCID 57863464, 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 (0.190 g, 0.452 mmol) and 4-Dimethylaminomethyl-5-(1-methyl-cyclopropyl)-thiazol-2-ylamine (0.105 g, 0.497 mmol) in DMF (4 mL). Add N,N-diisopropylethylamine (0.26 mL, 1.49 mmol), then O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.190 g, 0.500 mmol). The reaction mixture is stirred for 14 hours 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. 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. Wash the organic layer with aqueous saturated sodium chloride, dry over magnesium sulfate, filter, and concentrate to the title compound (0.054 g, 22%). MS (ES), n/z 541 (M+1).

Workup

  1. customPurify
  2. washeluting with 1:1 methanol
  3. customPurify via reverse phase chromatography
  4. customby 50.8 mm (i.d.) column w/10 micron particles (MeCN/0.03% HCl H2O (5:95) to 100% MeCN; 30 min)
  5. customPartition between ethyl acetate and 1 N NaOH
  6. washWash the organic layer with aqueous saturated sodium chloride
  7. dry with materialdry over magnesium sulfate
  8. filtrationfilter
  9. concentrationconcentrate to the title compound (0.054 g, 22%)

Sources & evidence

ORD record
ord-7c4ebe1c07204a3a806e7fc58f8ff273
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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