Sodium hydride → HCID 11612683, compound

HRID 550499Notes

Reaction equation

HRID 550499 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][CH3:30])[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.Br[CH2:32][CH2:33][CH2:34]C(Cl)=O.[H-].[Na+].CC(N(C)C)=[O:42]>>[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[CH2:34][CH2:33][CH2:32][C:30]4=[O:42])[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

5

Reactant 4

HCID 24758Sodium hydrideHCID 31374DimethylacetamideHCID 702254-Bromobutyryl chlorideHCID 11597061HCID 11597061, compound

Product 1

HCID 11612683HCID 11612683, compoundYield 9%

Procedure

N-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]-3-[2-(methylamino)ethoxy]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (prepared as described in Example 24/50 mg, 0.12 mmol) was dissolved in DMA (1 ml) and 4-bromobutyryl chloride (14 μl, 0.12 mmol) was added drop-wise at −15° C. After 1 hour at room temperature, sodium hydride (60%, 29 mg) was added to the mixture and stirring was continued for 3 hours. The reaction was quenched with water and the crude product was purified by preparative HPLC (column beta-basic, Hypercil 5 μm, 21×100 mm) eluting with a mixture of water and acetonitrile containing 2g/l of ammonium carbonate (gradient) to give the title compound (5 mg, 9%); NMR Spectrum: 1.90-1.95 (m, 2H), 2.25 (t, 2H), 3.47 (t, 2H), 3.68 (br s, 2H), 4.39 (br s, 2H), 5.28 (s, 2H), 7.25 (d, 1H), 7.36 (t, 1H), 7.57 (d, 1H), 7.80-7.89 (m, 2H), 8.16 (br s, 2H), 8.32 (s, 1H), 8.59 (d, 1H); Mass Spectrum: 480 (MH+).

Workup

  1. waitwas continued for 3 hours
  2. customThe reaction was quenched with water
  3. customthe crude product was purified by preparative HPLC (column beta-basic, Hypercil 5 μm, 21×100 mm)
  4. washeluting with a mixture of water and acetonitrile containing 2g/l of ammonium carbonate (gradient)

Sources & evidence

ORD record
ord-f79720e5174e45258ea15d300a54e4ef
Source dataset
uspto-grants-2011_05
Patent number
US07947676B2

Reaction notes

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