Sodium t-butoxide → HCID 67285558, compound

HRID 1618712Notes

Reaction equation

HRID 1618712 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]3[NH:15][CH2:14][C:13]4([CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[C:10]3=[N:11][CH:12]=2)[CH2:3][CH2:2]1.Cl[C:22]1[C:31]2[C:26](=[CH:27][C:28]([F:32])=[CH:29][CH:30]=2)[N:25]=[C:24]([N:33]2[CH2:38][CH2:37][CH2:36][CH2:35][C:34]2=[O:39])[C:23]=1[CH3:40].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:32][C:28]1[CH:27]=[C:26]2[C:31]([C:22]([N:15]3[C:9]4[C:10](=[N:11][CH:12]=[C:7]([N:4]5[CH2:5][CH2:6][O:1][CH2:2][CH2:3]5)[CH:8]=4)[C:13]4([CH2:20][CH2:19][O:18][CH2:17][CH2:16]4)[CH2:14]3)=[C:23]([CH3:40])[C:24]([N:33]3[CH2:38][CH2:37][CH2:36][CH2:35][C:34]3=[O:39])=[N:25]2)=[CH:30][CH:29]=1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]HCID 67284990HCID 67284990, compound

Product 1

HCID 67285558HCID 67285558, compound

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by stirring 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (56.4 mg, 0.20 mmol), 1-(4-chloro-7-fluoro-3-methylquinolin-2-yl)piperidin-2-one (60 mg, 0.20 mmol), sodium tert-butoxide (39.4 mg, 0.41 mmol) and XPhos precatalyst (15.1 mg, 0.020 mmol) in toluene (1.5 mL) at 130° C. for 1 h and 15 min in a microwave reactor. Purification by column chromatography (DCM: (DCM:MeOH:NH4OH, 9:1:0.4) from 1:0 to 7:3) gave the desired product. Further purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave 1-(7-fluoro-3-methyl-4-(6′-(4-morpholinyl)-2,3,5,6-tetrahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridin]-1′(2′H)-yl)-2-quinolinyl)-2-piperidinone. 1H NMR (500 MHz, chloroform-d) δ ppm 7.59-7.84 (3H, m), 7.20-7.33 (1H, m), 6.02-5.69 (1H, m), 4.10-4.34 (3H, m), 3.88-4.08 (1H, m), 3.71-3.82 (4H, m), 3.41-3.64 (4H, m), 2.91-3.15 (4H, m), 2.53-2.68 (2H, m), 2.28-2.41 (2H, m), 1.98-2.18 (7H, m), 1.78-1.87 (2H, m). Mass Spectrum (ESI) m/e=532.2 (M+1).

Workup

  1. customPrepared
  2. custom15 min
  3. customPurification by column chromatography (DCM: (DCM:MeOH:NH4OH, 9:1:0.4) from 1:0 to 7:3)

Sources & evidence

ORD record
ord-a80599be13b34c30aaa9d8097ffed59d
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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