Hydrochloric Acid → N-(2-fluoro-5-[2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzyl)-N',N'-dimethyl-ethane-1,2-diamine hydrochloride

HRID 216114Notes

Reaction equation

HRID 216114 reaction equation
[F:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[C:14]([NH:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=3)[N:13]=[C:12]([O:27][CH3:28])[N:11]=2)=[CH:6][C:3]=1[CH:4]=O.[CH3:29][N:30]([CH2:32][CH2:33][NH2:34])[CH3:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:49]>C(Cl)Cl.CO.CCOC(C)=O>[ClH:49].[F:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[C:14]([NH:16][CH2:17][CH2:18][C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[N:13]=[C:12]([O:27][CH3:28])[N:11]=2)=[CH:6][C:3]=1[CH2:4][NH:34][CH2:33][CH2:32][N:30]([CH3:31])[CH3:29]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 66053N,N-DimethylethylenediamineHCID 5049666Sodium triacetoxyborohydrideHCID 115817192-Fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzaldehyde

Product 1

HCID 69068669N-(2-fluoro-5-[2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzyl)-N',N'-dimethyl-ethane-1,2-diamine hydrochlorideYield 92%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzaldehyde [275 mg, 072 mmol, Example 35(j)], unsym-dimethylethylenediamine (217 μL, 1.97 mmol), sodium triacetoxyborohydride (500 mg, 2.36 mmol) and 3 Å sieves (500 mg) in DCM (7 mL) is stirred at room temperature under a nitrogen atmosphere for 5 hours. The reaction mixture is filtered and the filter cake is washed with DCM (50 mL). The combined filtrate and washings are extracted water with (50 mL) and the aqueous is extracted with DCM (50 mL). The new organic extract is washed with water (30 mL), with brine (30 mL), dried over sodium sulfate, filtered and concentrated by rotary evaporator. The resulting solid is subjected to flash column chromatography on silica (4.5 g) eluting with 0 to 7% MeOH in DCM gradient to afford a solid that is dissolved in methanol. This solution is treated with hydrogen chloride in EtOAc and concentrated to afford N-(2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzyl)-N′,N′-dimethyl-ethane-1,2-diamine hydrochloride [300 mg, 92%, Example 13(d)]. LCMS: RT=2.04 minutes, MS: 454 (M+H). IC50=56 nM

Workup

  1. filtrationThe reaction mixture is filtered
  2. washthe filter cake is washed with DCM (50 mL)
  3. extractionThe combined filtrate and washings are extracted water with (50 mL)
  4. extractionthe aqueous is extracted with DCM (50 mL)
  5. extractionThe new organic extract
  6. washis washed with water (30 mL), with brine (30 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated by rotary evaporator
  10. washeluting with 0 to 7% MeOH in DCM gradient
  11. customto afford a solid
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-ad2b8edfd1a04530b51bf4a240fa64c4
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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