Sodium Carbonate → (R)-5-(4-(2-(3,5-difluorophenyl)-1-(2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamido)ethyl)-2-((2-methoxyethyl)amino)pyrimidin-5-yl)-2-fluorobenzamide

HRID 2170326Notes

Reaction equation

HRID 2170326 reaction equation
Br[C:2]1[C:3]([C@H:13]([NH:23][C:24](=[O:39])[CH2:25][N:26]2[C:34]3[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=3[C:28]([C:35]([F:38])([F:37])[F:36])=[N:27]2)[CH2:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[C:17]([F:22])[CH:16]=2)=[N:4][C:5]([NH:8][CH2:9][CH2:10][O:11][CH3:12])=[N:6][CH:7]=1.[C:40]([C:43]1[CH:44]=[C:45](B(O)O)[CH:46]=[CH:47][C:48]=1[F:49])(=[O:42])[NH2:41].[Li+].[Cl-].C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.COCCOC.CN(C=O)C.O>[F:22][C:17]1[CH:16]=[C:15]([CH2:14][C@H:13]([C:3]2[C:2]([C:45]3[CH:46]=[CH:47][C:48]([F:49])=[C:43]([CH:44]=3)[C:40]([NH2:41])=[O:42])=[CH:7][N:6]=[C:5]([NH:8][CH2:9][CH2:10][O:11][CH3:12])[N:4]=2)[NH:23][C:24](=[O:39])[CH2:25][N:26]2[C:34]3[CH2:33][CH2:32][CH2:31][CH2:30][C:29]=3[C:28]([C:35]([F:36])([F:38])[F:37])=[N:27]2)[CH:20]=[C:19]([F:21])[CH:18]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 44717530(3-Carbamoyl-4-fluorophenyl)boronic acidHCID 90281480(R)-N-(1-(5-bromo-2-((2-methoxyethyl)amino)pyrimidin-4-yl)-2-(3,5-difluorophenyl)ethyl)-2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamide

Product 1

HCID 90290144(R)-5-(4-(2-(3,5-difluorophenyl)-1-(2-(3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)acetamido)ethyl)-2-((2-methoxyethyl)amino)pyrimidin-5-yl)-2-fluorobenzamide

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 131732935Dme dmf H2OSolvent

Conditions

Temperature
150 °C

Procedure

In a microwave tube were charged with compound 11I (29 mg, 0.1 mmol), (3-carbamoyl-4-fluorophenyl)boronic acid (27 mg, 0.15 mmol), LiCl (13 mg, 0.3 mmol), Na2CO3 (17 mg, 0.2 mmol), Pd(PPh3)2Cl2 (3.5 mg, 0.005 mmol). To the mixture was added 2 mL of DME/DMF/H2O (4/1/1). The mixture was heated up to 150° C. for 30 min in a Microwave Synthesizer. After cooled down and filtered through a syringe filter, purified on reverse phase HPLC eluting with acetonitrile and water (with 0.1% TFA) to afford the title product. 1H NMR (400 MHz, CD3OD) δ 8.61 (d, J=8.0 Hz, 1H), 8.07 (s, 1H), 7.48 (dd, J=6.9, 2.3 Hz, 1H), 7.40-7.33 (m, 1H), 7.22 (dd, J=10.7, 8.5 Hz, 1H), 6.70 (t, J=9.2 Hz, 1H), 6.45 (d, J=6.2 Hz, 2H), 5.24 (q, J=7.5 Hz, 1H), 4.76 (s, 2H), 3.85-3.56 (m, 4H), 3.41 (s, 3H), 3.01 (ddd, J=29.2, 13.3, 7.4 Hz, 2H), 2.63-2.34 (m, 4H), 1.88-1.60 (m, 4H). MS (m/z) 676.46 [M+H]+.

Workup

  1. temperatureAfter cooled down
  2. filtrationfiltered through a syringe
  3. filtrationfilter
  4. custompurified on reverse phase HPLC
  5. washeluting with acetonitrile and water (with 0.1% TFA)

Sources & evidence

ORD record
ord-e1ed7ca5265848f39598c4b5307fb83b
Source dataset
uspto-grants-2015_06
Patent number
US09050344B2

Reaction notes

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