Sodium Carbonate → HCID 68512115, compound

HRID 2241266Notes

Reaction equation

HRID 2241266 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:29]([C:31]2[C:32](=[O:44])[N:33]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[N:34]=[CH:35][CH:36]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:16]=[C:17](I)[C:10]=12.[N:45]1([C:51]([C:53]2[CH:58]=[CH:57][C:56](B(O)O)=[CH:55][CH:54]=2)=[O:52])[CH2:50][CH2:49][O:48][CH2:47][CH2:46]1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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>[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:29]([C:31]2[C:32](=[O:44])[N:33]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)[N:34]=[CH:35][CH:36]=2)=[O:30])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:16]=[C:17]([C:56]3[CH:55]=[CH:54][C:53]([C:51]([N:45]4[CH2:50][CH2:49][O:48][CH2:47][CH2:46]4)=[O:52])=[CH:58][CH:57]=3)[C:10]=12

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2773546[4-(Morpholine-4-carbonyl)phenyl]boronic acidHCID 68513145HCID 68513145, compound

Product 1

HCID 68512115HCID 68512115, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a small round bottom flask was added N-(3-fluoro-4-(3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (30 mg, 0.0425 mmol), 4-(morpholine-4-carbonyl)phenylboronic acid (20.0 mg, 0.0849 mmol), and Pd(PPh3)4 (2.45 mg, 0.00212 mmol) and the mixture was dissolved in 3:1 DME:aqueous 2N Na2CO3 (2 mL). The mixture was stirred at 70° C. until the reaction was determined to be complete by LC/MS (1-18 hours). The reaction mixture was then partitioned between ethyl acetate (15 mL) and water (30 mL). The organic layer washed with brine, dried over Na2SO4 and evaporated to afford crude product. Purified by silica gel column chromatography (Biotage 12M) eluting with 1-5% MeOH/CHCl3 to give the desired product. Yield: 40.2 mg, 81%. LRMS (APCI pos) m/e 770.1 (M+H).

Workup

  1. customto be complete by LC/MS (1-18 hours)
  2. customThe reaction mixture was then partitioned between ethyl acetate (15 mL) and water (30 mL)
  3. washThe organic layer washed with brine
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customto afford crude product
  7. customPurified by silica gel column chromatography (Biotage 12M)
  8. washeluting with 1-5% MeOH/CHCl3

Sources & evidence

ORD record
ord-7fe9fe47450848eeb8b75b6dcc07516e
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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