Sodium t-butoxide → 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-(3-fluorophenyl)-3-methyl-1,8-naphthyridine

HRID 1618762Notes

Reaction equation

HRID 1618762 reaction equation
Cl[C:2]1[C:11]2[C:6](=[N:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=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](=[N:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=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 672853774-Chloro-2-(3-fluorophenyl)-3-methyl-1,8-naphthyridine

Product 1

HCID 672857444-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-(3-fluorophenyl)-3-methyl-1,8-naphthyridine

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y using 4-chloro-2-(3-fluorophenyl)-3-methyl-1,8-naphthyridine (70.1 mg, 0.257 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (60 mg, 0.257 mmol), sodium tert-butoxide (49.4 mg, 0.514 mmol) and XPhos precatalyst (18.9 mg, 0.026 mmol) in toluene (4 mL) for 2 hours at 110° C. 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-(3-fluorophenyl)-3-methyl-1,8-naphthyridine. 1H NMR (400 MHz, chloroform-d) δ ppm 9.12 (1H, dd, J=4.3, 2.0 Hz), 8.17 (1H, dd, J=8.4, 2.0 Hz), 7.64 (1H, d, J=2.3 Hz), 7.42-7.54 (4H, m), 7.13-7.23 (1H, m), 5.79 (1H, d, J=2.3 Hz), 3.86-3.91 (1H, m), 3.80-3.84 (1H, m), 3.72-3.79 (4H, m), 2.94-3.05 (4H, m), 2.37 (3H, s), 1.58 (3H, s), 1.53 (3H, s). Mass Spectrum (ESI) m/e=470.2 (M+1)

Workup

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

Sources & evidence

ORD record
ord-92035fb34f374aa6925086daa972d8b2
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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