Sodium t-butoxide → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-(5-fluoro-3-pyridinyl)-3-methyl-1,7-naphthyridine

HRID 1618780Notes

Reaction equation

HRID 1618780 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][N:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:13]=[N:14][CH:15]=[C:16]([F:18])[CH:17]=2)[C:3]=1[CH3:19].[CH3:20][C:21]1([CH3:36])[C:25]2=[N:26][CH:27]=[C:28]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH:29]=[C:24]2[NH:23][CH2:22]1.CC(C)([O-])C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C1(C)C=CC=CC=1>[CH3:20][C:21]1([CH3:36])[C:25]2=[N:26][CH:27]=[C:28]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH:29]=[C:24]2[N:23]([C:2]2[C:11]3[C:6](=[CH:7][N:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([F:18])[CH:17]=3)[C:3]=2[CH3:19])[CH2:22]1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholineHCID 672851084-Chloro-2-(5-fluoropyridin-3-yl)-3-methyl-1,7-naphthyridine

Product 1

HCID 509392134-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-(5-fluoro-3-pyridinyl)-3-methyl-1,7-naphthyridine

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y using 4-chloro-2-(5-fluoropyridin-3-yl)-3-methyl-1,7-naphthyridine (100 mg, 0.365 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (85 mg, 0.365 mmol), sodium tert-butoxide (70.2 mg, 0.731 mmol) and XPhos precatalyst (26.9 mg, 0.037 mmol) in toluene (4 mL) at 110° C. for 2 h. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-(5-fluoro-3-pyridinyl)-3-methyl-1,7-naphthyridine. 1H NMR (400 MHz, chloroform-d) δ ppm 9.52-9.64 (1H, m), 8.74 (1H, t, J=1.8 Hz), 8.63 (1H, d, J=2.7 Hz), 8.59 (1H, d, J=5.9 Hz), 7.76-7.82 (1H, m), 7.67 (1H, d, J=2.3 Hz), 7.55-7.59 (1H, m), 5.84 (1H, d, J=2.3 Hz), 3.81-3.93 (2H, m), 3.70-3.79 (4H, m), 2.95-3.07 (4H, m), 2.40 (3H, s), 1.60 (3H, s), 1.54 (3H, s). Mass Spectrum (ESI) m/e=471.2 (M+1).

Workup

  1. customPrepared
  2. customat 110° C.
  3. customfor 2 h
  4. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

Sources & evidence

ORD record
ord-38c93c32d2b741bd82b631f3ef075188
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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