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

HRID 1618735Notes

Reaction equation

HRID 1618735 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]=[CH:14][N:13]=2)[C:3]=1[CH3:18].[CH3:19][C:20]1([CH3:35])[C:24]2=[N:25][CH:26]=[C:27]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)[CH:28]=[C:23]2[NH:22][CH2:21]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>[CH3:19][C:20]1([CH3:35])[C:24]2=[N:25][CH:26]=[C:27]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)[CH:28]=[C:23]2[N:22]([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]=[CH:14][N:13]=3)[C:3]=2[CH3:18])[CH2:21]1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596310684-Chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridineHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholine

Product 1

HCID 672846924-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo-[3,2-b]pyridin-1-yl)-3-methyl-2-(2-pyridinyl)-1,8-naphthyridine

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by using 4-chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine (40 mg, 0.156 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo-[3,2-b]pyridin-6-yl)morpholine (36.5 mg, 0.156 mmol), XPhos precatalyst (11.5 mg, 0.015 mmol) and sodium tert-butoxide (30 mg, 0.313 mmol) in toluene (4 mL) for 2 h at 110° C. Purification by reverse phase HPLC (10 to 50% acetonitrile in water) gave 4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo-[3,2-b]pyridin-1-yl)-3-methyl-2-(2-pyridinyl)-1,8-naphthyridine. 1H NMR (400 MHz, chloroform-d) δ ppm 9.12 (1H, dd, J=4.1, 2.0 Hz), 8.71 (1H, ddd, J=4.8, 1.9, 1.0 Hz), 8.14-8.21 (2H, m), 7.92 (1H, td, J=7.7, 1.8 Hz), 7.62 (1H, d, J=2.3 Hz), 7.37-7.48 (2H, m), 5.82 (1H, d, J=2.3 Hz), 3.86-3.91 (1H, m), 3.69-3.82 (5H, m), 2.93-3.04 (4H, m), 2.50 (3H, s), 1.58 (3H, s), 1.53 (3H, s). Mass Spectrum (ESI) m/e=453.2 (M+1).

Workup

  1. customPrepared
  2. customfor 2 h
  3. customat 110° C
  4. customPurification by reverse phase HPLC (10 to 50% acetonitrile in water)

Sources & evidence

ORD record
ord-234f84e4ebbb4d3183eb7b3c3c275b7f
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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