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

HRID 1618745Notes

Reaction equation

HRID 1618745 reaction equation
[CH3:1][C:2]1([CH3:17])[C:6]2=[N:7][CH:8]=[C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH:10]=[C:5]2[NH:4][CH2:3]1.Cl[C:19]1[C:28]2[C:23](=[N:24][CH:25]=[CH:26][CH:27]=2)[N:22]=[C:21]([C:29]2[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][N:30]=2)[C:20]=1[CH3:36].CC(C)([O-])C.[Na+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1(C)C=CC=CC=1>[CH3:1][C:2]1([CH3:17])[C:6]2=[N:7][CH:8]=[C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[CH:10]=[C:5]2[N:4]([C:19]2[C:28]3[C:23](=[N:24][CH:25]=[CH:26][CH:27]=3)[N:22]=[C:21]([C:29]3[CH:34]=[C:33]([CH3:35])[CH:32]=[CH:31][N:30]=3)[C:20]=2[CH3:36])[CH2:3]1

Participants

6

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 672844994-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)-morpholineHCID 672846184-Chloro-3-methyl-2-(4-methylpyridin-2-yl)-1,8-naphthyridine

Product 1

HCID 672846054-(3,3-dimethyl-6-(4-morpholinyl)-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-3-methyl-2-(4-methyl-2-pyridinyl)-1,8-naphthyridine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y using 4-(3,3-dimethyl-2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-6-yl)morpholine (18 mg, 0.077 mmol), 4-chloro-3-methyl-2-(4-methylpyridin-2-yl)-1,8-naphthyridine (20.81 mg, 0.077 mmol), sodium tert-butoxide (14.86 mg, 0.154 mmol) and XPhos (7.72 mmol, 7.72 mol) 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)-3-methyl-2-(4-methyl-2-pyridinyl)-1,8-naphthyridine. 1H NMR (400 MHz, chloroform-d) δ ppm 9.12 (1H, dd, J=4.3, 2.0 Hz), 8.57 (1H, d, J=5.1 Hz), 8.17 (1H, dd, J=8.2, 2.0 Hz), 8.00-8.03 (1H, m), 7.61 (1H, d, J=2.3 Hz), 7.44 (1H, dd, J=8.3, 4.2 Hz), 7.22 (1H, ddd, J=5.1, 1.8, 0.8 Hz), 5.81 (1H, d, J=2.3 Hz), 3.86-3.90 (1H, m), 3.77-3.82 (1H, m), 3.72-3.77 (4H, m), 2.93-3.04 (4H, m), 2.50 (3H, s), 2.49 (3H, s), 1.58 (3H, s), 1.53 (3H, s). Mass Spectrum (ESI) m/e=467.2 (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-97fbb71e8e1f45088b484e11e4107f24
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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