Lithium Chloride → 2-(cyclohexylmethyl)-5-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(4-(morpholine-4-carbonyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methylpyrimidin-4(3H)-one

HRID 2241310Notes

Reaction equation

HRID 2241310 reaction equation
[CH:1]1([CH2:7][C:8]2[N:13]([CH3:14])[C:12](=[O:15])[C:11]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][N:26]=[C:25]5[N:29]([CH2:33][C:34]6[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=6)[N:30]=[C:31](I)[C:24]=45)=[C:18]([F:42])[CH:17]=3)=[CH:10][N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:43]1([C:49]([C:51]2[CH:56]=[CH:55][C:54](B(O)O)=[CH:53][CH:52]=2)=[O:50])[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([CH2:7][C:8]2[N:13]([CH3:14])[C:12](=[O:15])[C:11]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][N:26]=[C:25]5[N:29]([CH2:33][C:34]6[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=6)[N:30]=[C:31]([C:54]6[CH:53]=[CH:52][C:51]([C:49]([N:43]7[CH2:48][CH2:47][O:46][CH2:45][CH2:44]7)=[O:50])=[CH:56][CH:55]=6)[C:24]=45)=[C:18]([F:42])[CH:17]=3)=[CH:10][N:9]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 2773546[4-(Morpholine-4-carbonyl)phenyl]boronic acidHCID 685170452-(cyclohexylmethyl)-5-(3-fluoro-4-(3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methylpyrimidin-4(3H)-one

Product 1

HCID 685153872-(cyclohexylmethyl)-5-(3-fluoro-4-(1-(4-methoxybenzyl)-3-(4-(morpholine-4-carbonyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methylpyrimidin-4(3H)-oneYield 98.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 2-(cyclohexylmethyl)-5-(3-fluoro-4-(3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-3-methylpyrimidin-4(3H)-one (0.025 g, 0.037 mmol), 4-(morpholine-4-carbonyl)phenylboronic acid (0.010 g, 0.044 mmol), Pd(PPh3)4 (0.002 g, 0.002 mmol) and lithium chloride (0.006 g, 0.147 mmol) in dioxane (1 mL) and 2 M aqueous Na2CO3 (1 mL) was stirred at 100° C. for 35 minutes and then at room temperature overnight. The reaction mixture was partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated to yield 0.027 g crude product as a yellow gum. The crude material was used without further purification in the following step. LRMS (APCI pos) m/e 743 (M+1).

Workup

  1. customat room temperature
  2. customovernight
  3. customThe reaction mixture was partitioned between EtOAc and H2O
  4. customThe layers were separated
  5. extractionthe aqueous layer was re-extracted with EtOAc (1×)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-fa170be939db43efad23a5f722c5ec98
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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