Sodium Carbonate → HCID 22347123, compound

HRID 2056028Notes

Reaction equation

HRID 2056028 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][CH2:13][OH:14])[N:9]=[C:10](I)[C:3]=12.[CH3:15][O:16][C:17]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[CH:19][C:18]=1[NH:32][C:33](=[O:45])[C:34]1[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][C:35]=1[F:44].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][CH2:13][OH:14])[N:9]=[C:10]([C:21]3[CH:20]=[CH:19][C:18]([NH:32][C:33](=[O:45])[C:34]4[CH:39]=[CH:38][C:37]([C:40]([F:42])([F:43])[F:41])=[CH:36][C:35]=4[F:44])=[C:17]([O:16][CH3:15])[CH:22]=3)[C:3]=12

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 22346783HCID 22346783, compound2×HCID 22347319N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-(trifluoromethyl)benzamide

Product 1

HCID 22347123HCID 22347123, compoundYield 64.6%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-ethanol (Intermediate 3) (0.120 g, 0.393 mmol), N1-[2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-fluoro-4-(trifluoromethyl)benzamide (0.190 g, 0.433 mmol), palladium tetrakis(triphenylphosphine) (0.045 g, 0.039 mmol), and sodium carbonate (0.100 g, 0.943 mmol) in DME (3.9 mL) and water (3.9 mL) was heated at 85° C. for 3 h. The reaction mixture was cooled to ambient temperature and the organic solvent was removed in vacuo. The precipitate was collected by filtration, rinsed with water (20 mL) and ether (20 mL), and dried in vacuo to afford N1-{4-[4-amino-1-(2-hydroxyethyl)-1H-pyrazolo [3,4-d]pyrimidin-3-yl]-2-methoxyphenyl}-2-fluoro-4-(trifluoromethyl)benzamide as a brown solid (0.125 g, 0.254 mmol): 1H NMR (d6-DMSO, 400 MHz): δH 9.89 (1H, d, J=4.0 Hz), 8.31 (1H, d, J=8.0 Hz), 8.25 (1H, s), 7.99 (1H, t, J=7.4 Hz), 7.89 (1H, d, J=10.4 Hz), 7.75 (1H, d, J=8.0 Hz), 7.34 (1H, s), 7.31 (1H, d, J=8.4 Hz), 4.89 (1H, s), 4.40 (2H, t, J=5.6 Hz), 3.94 (3H, s), and 3.86 (2H, t, J=5.6 Hz); RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile—0.1 M ammonium acetate over 15 min, 1 mL/min). Rt 9.85 min. MS: MH+491.

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customthe organic solvent was removed in vacuo
  3. filtrationThe precipitate was collected by filtration
  4. washrinsed with water (20 mL) and ether (20 mL)
  5. customdried in vacuo

Sources & evidence

ORD record
ord-d1d543d147534797991675c3237acf67
Source dataset
uspto-grants-2008_02
Patent number
US07332497B2

Reaction notes

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