Ammonium Chloride → HCID 66600223, compound

HRID 1621813Notes

Reaction equation

HRID 1621813 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].F[C:12]1[C:17]([C:18]2[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=3)[CH2:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[CH:19]=2)=[CH:16][C:15]([CH:44]([N:46]2[CH2:51][CH2:50][O:49][CH2:48][CH2:47]2)[CH3:45])=[CH:14][N:13]=1.[F:52][C:53]1[CH:54]=[C:55]([NH2:61])[CH:56]=[N:57][C:58]=1[O:59][CH3:60].[NH4+].[Cl-]>C1COCC1>[F:52][C:53]1[CH:54]=[C:55]([NH:61][C:12]2[C:17]([C:18]3[N:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25]([CH2:26][C:27]4[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=4)[CH2:35][C:36]4[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=4)[CH:19]=3)=[CH:16][C:15]([CH:44]([N:46]3[CH2:51][CH2:50][O:49][CH2:48][CH2:47]3)[CH3:45])=[CH:14][N:13]=2)[CH:56]=[N:57][C:58]=1[O:59][CH3:60]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium Hexamethyldisilazide2×HCID 454803515-Fluoro-6-methoxypyridin-3-amine2×HCID 66600058HCID 66600058, compound

Product 1

HCID 66600223HCID 66600223, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium bis(trimethylsilyl)amide (1.0 M solution in hexane, 0.592 mL, 0.592 mmol) was added to a solution of 6-(2-fluoro-5-(1-(4-morpholinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.110 g, 0.197 mmol) and 5-fluoro-6-methoxypyridin-3-amine (0.042 g, 0.296 mmol, Anichem, North Brunswick, N.J.) in THF (1.5 mL) at −10° C. After 1 h, more lithium bis(trimethylsilyl)amide (1.0 M solution in hexane, 0.592 mL, 0.592 mmol) and 5-fluoro-6-methoxypyridin-3-amine (0.042 g, 0.296 mmol) were added. After a further 1 h, saturated NH4Cl (aq.) was added. The mixture was extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was adsorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 100% EtOAc in hexane to give 6-(2-((5-fluoro-6-methoxy-3-pyridinyl)amino)-5-(1-(4-morpholinyl)ethyl)-3-pyridinyl)-N,N-bis(4-methoxybenzyl)-2-methyl-4-pyrimidinamine (0.104 g, 0.153 mmol, 78% yield) as a brown oil. 1H NMR (400 MHz, CDCl3) δ 11.92 (s, 1H); 8.26 (dd, J=12.72, 2.35 Hz, 1H); 8.11 (d, J=2.15 Hz, 1H); 8.02 (d, J=2.35 Hz, 1H); 7.56-7.61 (m, 1H); 7.18 (dd, J=8.61, 0.98 Hz, 4H); 6.82-6.91 (m, 4H); 6.53 (s, 1H); 4.80 (br s, 4H); 4.01 (s, 3H); 3.79 (s, 6H); 3.62 (t, J=4.69 Hz, 4H); 3.30 (q, J=6.65 Hz, 1H); 2.66 (s, 3H); 2.39-2.47 (m, 2H); 2.30-2.37 (m, 2H); 1.31 (d, J=6.85 Hz, 3H). m/z (ESI, +ve) 680.2 (M+H)+.

Workup

  1. waitAfter a further 1 h
  2. extractionThe mixture was extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  7. washeluting with a gradient of 0% to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-051d642a7c5d4ff2b8a67c1977133e5a
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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