Triethylamine → HCID 11684682, compound

HRID 550495Notes

Reaction equation

HRID 550495 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[NH:23][N:24]=[C:25]([O:26][CH2:27][CH2:28][NH:29][CH2:30][CH2:31][OH:32])[C:18]=23)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1.C(N([CH2:38][CH3:39])CC)C.ClCC(OC(=O)CCl)=[O:43].[H-].[Na+]>CC(N(C)C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:16][C:17]2[N:22]=[CH:21][N:20]=[C:19]3[NH:23][N:24]=[C:25]([O:26][CH2:27][CH2:28][N:29]4[CH2:39][CH2:38][O:32][CH2:31][C:30]4=[O:43])[C:18]=23)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10946Chloroacetic anhydrideHCID 24758Sodium hydrideHCID 11532615HCID 11532615, compound

Product 1

HCID 11684682HCID 11684682, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

2-({2-[(4-{[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]amino}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)oxy]ethyl}amino)ethanol (prepared as described in Example 36/30 mg, 0.07 mmol) and triethylamine (10 μl) were dissolved in DMA (0.7 ml) and chloroacetic anhydride (12 mg, 0.07 mmol) was added at −15° C. The temperature was slowly raised to room temperature and the reaction mixture was stirred for 1 hour. Sodium hydride (60%, 16 mg) was then added and the reaction mixture was stirred for 1 hour. Water was then added and the mixture evaporated and purified by preparative HPLC (column beta-basic, Hypercil 5 □m, 21×100 mm) eluting with a mixture of water and acetonitrile containing 2g/l of ammonium carbonate (gradient) to give the title compound (8 mg, 24%); NMR Spectrum: 3.49 (t, 2H), 3.80-3.84 (m, 4H), 4.04 (s, 2H), 4.46 (t, 2H), 5.28 (s, 2H), 7.24 (d, 1H), 7.36 (t, 1H), 7.58 (d, 1H), 7.76 (dd, 1H), 7.88 (t, 2H), 8.12 (d, 1H), 8.19 (s, 1H), 8.32 (s, 1H), 8.59 (d, 1H); Mass Spectrum: 496 (MH+).

Workup

  1. stirringthe reaction mixture was stirred for 1 hour
  2. customthe mixture evaporated
  3. custompurified by preparative HPLC (column beta-basic, Hypercil 5 □m, 21×100 mm)
  4. washeluting with a mixture of water and acetonitrile containing 2g/l of ammonium carbonate (gradient)

Sources & evidence

ORD record
ord-520b1a01ccdb43ff982c3bd9e41f28db
Source dataset
uspto-grants-2011_05
Patent number
US07947676B2

Reaction notes

Loading…