Hydrochloric Acid → (6-{4-Fluoro-3-[(2-methoxy-ethylamino)-methyl]-phenyl}-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride

HRID 216113Notes

Reaction equation

HRID 216113 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][O:30][CH2:31][CH2:32][NH2:33].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[ClH:48]>C(Cl)Cl.CCOC(C)=O>[ClH:48].[F:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[C:12]([O:27][CH3:28])[N:13]=[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)[CH:15]=2)=[CH:6][C:3]=1[CH2:4][NH:33][CH2:32][CH2:31][O:30][CH3:29]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 80182-MethoxyethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 115817192-Fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzaldehyde

Product 1

HCID 69064238(6-{4-Fluoro-3-[(2-methoxy-ethylamino)-methyl]-phenyl}-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochlorideYield 75%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-fluoro-5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-benzaldehyde [300 mg, 0.787 mmol, Example 35(j)], 2-methoxyethylamine (170 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 with water (50 mL). The aqueous extract 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 8% MeOH in DCM gradient to afford a solid. This material is treated with hydrogen chloride in EtOAc and concentrated to afford (6-{4-fluoro-3-[(2-methoxy-ethylamino)-methyl]-phenyl}-2-methoxy-pyrimidin-4-yl)-[2-(4-methoxy-phenyl)-ethyl]-amine hydrochloride [260 mg, 75%, Example 13(b)] as a solid. LCMS: RT=1.98 minutes, MS: 441 (M+H). 1H NMR (300 MHz, CDCl3): δ 9.65 (1H, s), 8.27 (1H, s), 7.91 (1H, s), 7.47 (1H, t, J=0.03 Hz), 7.21 (2H, d, J=0.027 Hz), 6.85 (2H, d, J=0.027 Hz), 4.26 (2H, s), 4.03 (2H, s), 3.72 (6H, s), 3.31 (3H, s), 3.17 (2H, m), 2 (2H, t, J=0.024), 2.5 (2H, s).

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 with water (50 mL)
  4. extractionThe aqueous extract
  5. extractionis extracted with DCM (50 mL)
  6. extractionThe new organic extract
  7. washis washed with water (30 mL), with brine (30 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated by rotary evaporator
  11. washeluting with 0 to 8% MeOH in DCM gradient
  12. customto afford a solid
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-725a9d2326314040967b9e7079effd83
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

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