Sodium t-butoxide → 4-(1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine

HRID 1618726Notes

Reaction equation

HRID 1618726 reaction equation
[NH:1]1[CH2:6][CH2:5][S:4][C:3]2[N:7]=[CH:8][C:9]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:10][C:2]1=2.Cl[C:18]1[C:27]2[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=2)[N:21]=[C:20]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)[C:19]=1[CH3:35].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:28][C:24]1[CH:23]=[C:22]2[C:27]([C:18]([N:1]3[CH2:6][CH2:5][S:4][C:3]4[N:7]=[CH:8][C:9]([N:11]5[CH2:12][CH2:13][O:14][CH2:15][CH2:16]5)=[CH:10][C:2]3=4)=[C:19]([CH3:35])[C:20]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)=[N:21]2)=[CH:26][CH:25]=1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596310754-Chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 672845584-(2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine

Product 1

HCID 672846194-(1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine

Reagents, catalysts & solvents 2

HCID 54751079XPhos PalladacycleCatalystHCID 1140TolueneSolvent

Procedure

Prepared according to procedure Y by using 4-(2,3-dihydro-1H-pyrido[2,3-b]-[1,4]thiazin-7-yl)morpholine (43.5 mg, 0.18 mmol), 4-chloro-7-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (50 mg, 0.183 mmol), XPhos precatalyst (13.5 mg, 0.018 mmol) and sodium tert-butoxide (35.2 mg, 0.37 mmol) with heating in toluene (5 mL) for 1 h at 110° C. Purification by column chromatography (gradient of DCM to (DCM:MeOH:NH4OH, 90:9:1) from 1:0 to 9:1) gave 4-(1-(7-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine. Mass Spectrum (ESI) m/e=474.0 (M+1).

Workup

  1. customPrepared
  2. customPurification by column chromatography (gradient of DCM to (DCM:MeOH:NH4OH, 90:9:1) from 1:0 to 9:1)

Sources & evidence

ORD record
ord-887b3a241b164ab0b9adfa9b01c704ef
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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