Water → HCID 58529896, compound

HRID 1972747Notes

Reaction equation

HRID 1972747 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8](Br)[CH:9]=[C:10]([CH2:11][CH:12]3[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]3)[N:6]2[N:5]=[CH:4][N:3]=1.[CH2:24]([N:31]1[CH:39]=[C:38]2[C:33]([CH:34]=[C:35](B3OC(C)(C)C(C)(C)O3)[CH:36]=[CH:37]2)=[N:32]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C([O-])([O-])=O.[Na+].[Na+].O>CN(C=O)C.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>[NH2:1][C:2]1[C:7]2=[C:8]([C:35]3[CH:36]=[CH:37][C:38]4[C:33]([CH:34]=3)=[N:32][N:31]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH:39]=4)[CH:9]=[C:10]([CH2:11][CH:12]3[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 58529694HCID 58529694, compound

Product 1

HCID 58529896HCID 58529896, compoundYield 94.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

To a stirred, degassed mixture tert-butyl 3-[(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)methyl]azetidine-1-carboxylate (397 mg, 1.04 mmol), Intermediate C (521 mg, 1.56 mmol), Na2CO3 (330 mg, 3.12 mmol) and H2O (1.6 mL) in DMF (10 mL) was added tetrakis(triphenylphosphine)palladium(0) (120 mg, 0.10 mmol). The reaction was heated (110° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (50 mL) and H2O (50 mL). The layers were separated and the aqueous was further extracted with ethyl acetate (1×50 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated to dryness. The crude material was purified via ISCO® chromatography using a gradient of 50 to 75% ethyl acetate in hexanes to afford 500 mg (80%) of the desired product, which contained trace impurities.

Workup

  1. temperaturecooled to rt
  2. customThe mixture was partitioned between ethyl acetate (50 mL) and H2O (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous was further extracted with ethyl acetate (1×50 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to dryness
  8. customThe crude material was purified via ISCO® chromatography

Sources & evidence

ORD record
ord-164845d2d6f543bc96769a2ad49becc5
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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