Sodium t-butoxide → 2-(3,5-difluorophenyl)-4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-3-methyl-1,8-naphthyridine

HRID 1618746Notes

Reaction equation

HRID 1618746 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]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)[C:3]=1[CH3:20].[CH3:21][C:22]1([CH3:37])[C:26]2=[N:27][CH:28]=[C:29]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:30]=[C:25]2[NH:24][CH2:23]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>[F:19][C:14]1[CH:13]=[C:12]([C:4]2[C:3]([CH3:20])=[C:2]([N:24]3[C:25]4[C:26](=[N:27][CH:28]=[C:29]([N:31]5[CH2:32][CH2:33][O:34][CH2:35][CH2:36]5)[CH:30]=4)[C:22]([CH3:37])([CH3:21])[CH2:23]3)[C:11]3[C:6](=[N:7][CH:8]=[CH:9][CH:10]=3)[N:5]=2)[CH:17]=[C:16]([F:18])[CH:15]=1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596315174-Chloro-2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridineHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholine

Product 1

HCID 672849652-(3,5-difluorophenyl)-4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-3-methyl-1,8-naphthyridine

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y using 4-chloro-2-(3,5-difluorophenyl)-3-methyl-1,8-naphthyridine (68 mg, 0.234 mmol), 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (54.6 mg, 0.234 mmol), sodium tert-butoxide (45 mg, 0.468 mmol) and XPhos precatalyst (17.1 mg, 0.023 mmol) in toluene (4 mL) for 2 hours at 110° C. Purification by reverse phase HPLC (10 to 60% acetonitrile in waiter) gave 2-(3,5-difluorophenyl)-4-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-3-methyl-1,8-naphthyridine. 1H NMR (400 MHz, chloroform-d) δ ppm 9.13 (1H, dd, J=4.3, 2.0 Hz), 8.17 (1H, dd, J=8.2, 2.0 Hz), 7.65 (1H, d, J=2.3 Hz), 7.45 (1H, dd, J=8.3, 4.2 Hz), 7.25-7.28 (2H, m), 6.91-6.98 (1H, m), 5.78 (1H, d, J=2.5 Hz), 3.86-3.91 (1H, m), 3.79-3.84 (1H, m), 3.71-3.78 (4H, m), 2.94-3.04 (4H, m), 2.37 (3H, s), 1.58 (3H, s), 1.53 (3H, s). Mass Spectrum (ESI) m/e=488.2 (M+1).

Workup

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

Sources & evidence

ORD record
ord-7f9741ed48344598a465607ae0d1cd34
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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