Water → HCID 89808151, compound

HRID 1478276Notes

Reaction equation

HRID 1478276 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]2[CH:10]=[CH:9][C:8]([N:11]3[CH2:16][CH2:15][N:14]([C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]3)=[N:7][C:6]=12.[F:23][C:24]1[CH:25]=[CH:26][C:27]([O:33][CH3:34])=[C:28](B(O)O)[CH:29]=1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[F:23][C:24]1[CH:29]=[CH:28][C:27]([O:33][CH3:34])=[C:26]([C:2]2[CH:3]=[N:4][N:5]3[CH:10]=[CH:9][C:8]([N:11]4[CH2:16][CH2:15][N:14]([C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]4)=[N:7][C:6]=23)[CH:25]=1

Participants

8

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27826735-Fluoro-2-methoxyphenylboronic acidHCID 86697433Isopropyl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate

Product 1

HCID 89808151HCID 89808151, compoundYield 372.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 312751,4-DioxaneSolvent

Procedure

Isopropyl 4-(3-bromopyrazolo[1,5-a]pyrimidin-5-yl)piperazine-1-carboxylate (2.86 g, 7.8 mmol), 5-fluoro-2-methoxyphenyl boronic acid (2.64 g, 15.5 mmol), potassium carbonate (3.22 g, 23.3 mmol), Pd(OAc)2 (35 mg, 0.155 mmol), and x-Phos (146 mg, 0.31 mmol) were taken up in 15 mL dioxane and 7 mL water under nitrogen and stirred at 80° C. for 2 hours. Reaction then cooled to room temperature, filtered through celited plug with ethyl acetate. Reduced in vacuo and run through an isco silica column with hexane:ethyl acetate 75-100%. Product plus desbromo co-elute, reduced in Vacuo. Product recrystallized 2 times from ethyl acetate:Hexane, washed with heptanes dried to get 12 g product. 1H NMR (400 MHz, DMSO-d6) δ 8.73 (d, J=7.78 Hz, 1H), 8.50 (s, 1H), 8.29 (dd, J=3.14, 11.17 Hz, 1H), 7.04 (dd, J=5.02, 9.03 Hz, 1H), 6.95 (dd, J=3.26, 7.78 Hz, 1H), 6.79 (d, J=8.03 Hz, 1H), 4.77-4.85 (m, 1H), 3.87 (s, 3H), 3.70-3.78 (m, 4H), 3.48-3.56 (m, 4H), 1.21 (d, J=6.27 Hz, 6H). LRMS (ESI) m/z 414 [(M+H)]+, calc'd for C21H24N5O3: 413.4.

Workup

  1. customReaction
  2. filtrationfiltered through celited plug with ethyl acetate
  3. customProduct recrystallized 2 times from ethyl acetate
  4. washHexane, washed with heptanes
  5. customdried

Sources & evidence

ORD record
ord-bd518bfcd273420892d7e2418f398b51
Source dataset
uspto-grants-2016_08
Patent number
US09403832B2

Reaction notes

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