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

HRID 1618728Notes

Reaction equation

HRID 1618728 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=2)[C:3]=1[CH3:20].[NH:21]1[CH2:26][CH2:25][S:24][C:23]2[N:27]=[CH:28][C:29]([N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[CH:30][C:22]1=2.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:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:21]3[CH2:26][CH2:25][S:24][C:23]4[N:27]=[CH:28][C:29]([N:31]5[CH2:32][CH2:33][O:34][CH2:35][CH2:36]5)=[CH:30][C:22]3=4)=[C:3]([CH3:20])[C:4]([C:13]3[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][N:14]=3)=[N:5]2)=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 23676156Sodium t-butoxideHCID 596310864-Chloro-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolineHCID 672845584-(2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine

Product 1

HCID 672849584-(1-(7-fluoro-3-methyl-2-(4-methylpyridin-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-chloro-7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (54 mg, 0.19 mmol), 4-(2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine (45 mg, 0.19 mmol), sodium tert-butoxide (36 mg, 0.38 mmol), XPhos precatalyst (14 mg, 0.019 mmol) in toluene (4 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 8:2) gave 4-(1-(7-fluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl)morpholine. Mass Spectrum (ESI) m/e=488.0 (M+1).

Workup

  1. customPrepared
  2. customfor 1 h
  3. customat 110° C
  4. customPurification by column chromatography (gradient of DCM to (DCM:MeOH:NH4OH, 90:9:1) from 1:0 to 8:2)

Sources & evidence

ORD record
ord-13e3233d7858488a87d458c26aaa9991
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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