Phthalimide, N-(2-formylethyl)- → 2-(3-((7-Methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)isoindoline-1,3-dione

HRID 1921993Notes

Reaction equation

HRID 1921993 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[CH:5]=[C:4]([C:14]2[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH3:21])[N:15]=2)[CH:3]=1.C(N(CC)C(C)C)(C)C.[O:31]=[C:32]1[C:40]2[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=2)[C:34](=[O:41])[N:33]1[CH2:42][CH2:43][CH:44]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(OCC)(=O)C.C(O)(=O)C>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6]([CH:5]=[C:4]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([NH:20][CH3:21])[N:15]=3)[CH:3]=[C:2]2[NH:1][CH2:44][CH2:43][CH2:42][N:33]2[C:34](=[O:41])[C:35]3[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=3)[C:32]2=[O:31])=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 75525Phthalimide, N-(2-formylethyl)-HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 583363954-(4-amino-6-methoxynaphthalen-2-yl)-N-methylpyrimidin-2-amine

Product 1

HCID 532581702-(3-((7-Methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)isoindoline-1,3-dioneYield 48.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a slurry of 4-(4-amino-6-methoxynaphthalen-2-yl)-N-methylpyrimidin-2-amine (150 mg, 0.42 mmol) in 1,2-dichloromethane (10 ml) was added N,N-diisopropylethylamine (250 μl) followed by acetic acid (0.5 ml), 3-(1,3-dioxoisoindolin-2-yl)propanal (140 mg) and sodium triacetoxyborohydride (200 mg). The mixture was stirred at room temperature for 24 hours before being poured into ethyl acetate (100 ml) washed with water (250 ml) and dried over anhydrous magnesium sulfate. Evaporation to dryness gave a yellow oil which was purified by silica gel chromatography eluting with 40-60% ethyl acetate in hexanes to yield 2-(3-((7-methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)isoindoline-1,3-dione 181 as a yellow foam (95 mg). 1H NMR (CDCl3) 400 MHz δ 8.34 (d, J=5.2 Hz, 1H), 7.87 (s, 1H), 7.86-7.83 (m, 3H), 7.8 (d, J=8.8 Hz, 1H), 7.75-7.71 (m, 2H), 7.34 (s, 1H), 7.31 (d, J=2.4 Hz, 1H), 7.18 (dd, J=2.4 and 8.8 Hz, 1H), 7.08 (d, J=4.8 Hz, 1H), 5.24 (m, 1H), 4.9 (m, 1H), 4.04 (s, 3H), 3.9 (t, J=6.0 Hz 2H), 3.5 (t, J=6.0 Hz, 2H), 3.11 (d, J=5.2 Hz, 3H), 2.24 (m, 2H), 2.2-2.14 (m, 2H), LCMS m/e 468 (M+H)

Workup

  1. washwashed with water (250 ml)
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customEvaporation to dryness
  4. customgave a yellow oil which
  5. customwas purified by silica gel chromatography
  6. washeluting with 40-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-60d5d820afa24b05bf7d5e2bef30f242
Source dataset
uspto-grants-2012_05
Patent number
US08173808B2

Reaction notes

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