Water → HCID 58529330, compound

HRID 1972832Notes

Reaction equation

HRID 1972832 reaction equation
[CH2:1]([N:8]1[CH:16]=[C:15]2[C:10]([CH:11]=[C:12](B3OC(C)(C)C(C)(C)O3)[CH:13]=[CH:14]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:26][C:27]1[C:32]2=[C:33](Br)[CH:34]=[C:35]([CH:36]3[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37]3)[N:31]2[N:30]=[CH:29][N:28]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>CN(C=O)C>[NH2:26][C:27]1[C:32]2=[C:33]([C:12]3[CH:13]=[CH:14][C:15]4[C:10]([CH:11]=3)=[N:9][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:16]=4)[CH:34]=[C:35]([CH:36]3[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37]3)[N:31]2[N:30]=[CH:29][N:28]=1

Participants

6

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 59231934HCID 59231934, compound

Product 1

HCID 58529330HCID 58529330, compoundYield 38.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred suspension of Intermediate C (2.62 g mg, 7.85 mmol) and tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)pyrrolidine-1-carboxylate (2.50 g, 6.54 mmol) in degassed DMF (6.7 mL) was added solid potassium phosphate (4.16 g, 19.62 mmol) followed by water (833 uL, 49 mmol). The reaction mixture was taken through three purge-fill cycles using nitrogen and vacuum. The reaction was then heated (100° C.) for 1 h and then cooled to rt. The mixture was partitioned between ethyl acetate (200 mL) and H2O (100 mL). The layers were separated and the organic layer was washed 6 times with brine to remove DMF (50 mL each), dried (Na2SO4), and concentrated to dryness. The crude residue was purified by ISCO® chromatography using a gradient of 50 to 100% ethyl acetate in dichloromethane to afford 1.27 g (38%) of the desired product as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.53 (s, 1 H), 7.93 (s, 1 H), 7.80 (d, 1 H), 7.59 (s, 1 H), 7.35-7.30 (m, 4H), 7.15 (d, 1 H), 6.66 (s, 1H), 5.64 (s, 2 H), 3.9-3.7 (m, 1 H), 3.50-3.30 (m, 4H), 2.42 (m, 1H), 2.13 (m, 1H), 1.38 (s, 9H); ES-MS m/z 510.3 [M+H]+, HPLC RT (min) 3.16.

Workup

  1. custompurge-fill cycles
  2. temperaturecooled to rt
  3. customThe mixture was partitioned between ethyl acetate (200 mL) and H2O (100 mL)
  4. customThe layers were separated
  5. washthe organic layer was washed 6 times with brine
  6. customto remove DMF (50 mL each)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated to dryness
  9. customThe crude residue was purified by ISCO® chromatography

Sources & evidence

ORD record
ord-f8058f02a3aa4a068656b51e6223ef9a
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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