Dimethylformamide → HCID 58529597, compound

HRID 1972822Notes

Reaction equation

HRID 1972822 reaction equation
[NH2:1][C:2]1[C:7]2=[C:8](Br)[CH:9]=[C:10]([CH:11]3[O:16][CH2:15][CH:14]4[CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20][N:13]4[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1.CN(C=O)C.[CH2:34]([N:41]1[CH:49]=[C:48]2[C:43]([CH:44]=[C:45](B3OC(C)(C)C(C)(C)O3)[CH:46]=[CH:47]2)=[N:42]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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.O>[NH2:1][C:2]1[C:7]2=[C:8]([C:45]3[CH:46]=[CH:47][C:48]4[C:43]([CH:44]=3)=[N:42][N:41]([CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:49]=4)[CH:9]=[C:10]([CH:11]3[O:16][CH2:15][CH:14]4[CH2:17][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:19][CH2:20][N:13]4[CH2:12]3)[N:6]2[N:5]=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 585293132-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-IndazoleHCID 58529596HCID 58529596, compound

Product 1

HCID 58529597HCID 58529597, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of tert-butyl 3-(4-amino-5-bromopyrrolo[2,1-f][1,2,4]triazin-7-yl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate (1.50 g, 3.31 mmol) and tetrakis(triphenylphosphine)palladium(0) (764 mg, 0.66 mmol), in degassed 1,4-dioxane (15 mL) and DMF (15 mL) was added 2-benzyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole (1.33 g, 3.97 mmol), K2CO3 (1.10 g, 7.94 mmol), and H2O (3.9 mL). The mixture was degassed and heated (100° C.) for 17 h and then cooled to rt. The mixture was partitioned between ethyl acetate (250 mL) and saturated aqueous K2CO3 solution (200 mL). The layers were separated and the organic phase was washed, dried (Na2SO4), and concentrated to dryness. The residue was purified by recrystallization from acetonitrile to obtain 750 mg (39%) of the desired product. 1H-NMR (DMSO-d6) 8.53 (s, 1H), 7.91 (s, 1H), 7.79 (d, 1H), 7.57 (s, 1H), 7.35-7.28 (m, 5H), 7.11 (d, 1H), 6.71 (s, 1H), 5.64 (s, 2H), 5.14-5.10 (m, 1H), 3.88-3.71 (m, 3H), 3.33-3.26 (m, 2H), 3.03-2.99 (m, 1H), 2.89-2.69 (m, 2H), 2.42-2.38 (m, 1H), 2.12-2.08 (m, 2H), 1.38 (s, 9H); LC-MS [M+H]+=581, RT=2.57 min.

Workup

  1. customThe mixture was degassed
  2. temperaturecooled to rt
  3. customThe mixture was partitioned between ethyl acetate (250 mL) and saturated aqueous K2CO3 solution (200 mL)
  4. customThe layers were separated
  5. washthe organic phase was washed
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by recrystallization from acetonitrile

Sources & evidence

ORD record
ord-aed888d7b92a4910a4dae3755c643a2b
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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