Triisopropyl borate → HCID 10382614, compound

HRID 902038Notes

Reaction equation

HRID 902038 reaction equation
Br[C:2]1[C:3]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[N:12]=2)=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=12.C([Li])(C)(C)C.B(OC(C)C)(OC(C)C)OC(C)C.FC(F)(F)C([NH:40][C:41]1[N:42]=[C:43]2[CH:48]=[CH:47][C:46](I)=[CH:45][N:44]2[CH:50]=1)=O>C1COCC1.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>[CH3:17][C:13]1[N:12]=[C:11]([C:3]2[C:2]([C:46]3[CH:47]=[CH:48][C:43]4[N:44]([CH:50]=[C:41]([NH2:40])[N:42]=4)[CH:45]=3)=[C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][N:5]3[N:4]=2)[CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 21531Triisopropyl borateHCID 110136782,2,2-trifluoro-N-(6-iodoimidazo[1,2-a]pyridin-2-yl)acetamideHCID 59700618HCID 59700618, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 10382614HCID 10382614, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

Stir 3-bromo-2-(6-methyl-pyridin-2-yl)-pyrazolo[1,5-a]pyridine (500 mg, 1.74 mmol) in THF (20 ml) at −60° C. and add t-butyl lithium (4 ml, 6.94 mmol, 1.7M in pentane). Stir for 1 hour, then add tri-isopropyl borate (1.2 ml, 5.2 mmol) and warm to 0° C. for 1 hour. Quench with 1M HCl (5 ml). Concentrate in vacuo and redissolve in a 2:1 toluene/methanol mixture (30 ml). Adjust to pH 8 with aqueous 2M Na2CO3. Add 100 mg Pd(PPh3)4 and 2,2,2-trifluoro-N-(6-iodo-imidazo[1,2-a]pyridin-2-yl)-acetamide (200 mg, 563 mmol) and heat to 90° C. for 18 hours. Acidify with 1M HCl and extract with ethyl acetate (3×100 ml). Neutralize aqueous layer with 5N NaOH and extract with ethyl acetate (3×100 ml). Concentrate organic layer in vacuo and purify on Silica gel (eluting with 70/30 Hexane/EtOAc). MS ES+ m/e 341.1 (M+1).

Workup

  1. customQuench with 1M HCl (5 ml)
  2. concentrationConcentrate in vacuo
  3. dissolutionredissolve in a 2:1 toluene/methanol mixture (30 ml)
  4. extractionAcidify with 1M HCl and extract with ethyl acetate (3×100 ml)
  5. extractionNeutralize aqueous layer with 5N NaOH and extract with ethyl acetate (3×100 ml)
  6. customConcentrate organic layer in vacuo and purify on Silica gel (eluting with 70/30 Hexane/EtOAc)

Sources & evidence

ORD record
ord-5ab9ddcb309e4828bdfbf2c6bc65916b
Source dataset
uspto-grants-2008_04
Patent number
US07365066B2

Reaction notes

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