3-(Bromomethyl)-1H-indazole, N1-BOC protected → HCID 86753595, compound

HRID 343184Notes

Reaction equation

HRID 343184 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:8]2[C:14](=[O:15])[CH2:13][C:12](=[O:16])[N:11]([CH2:17][C:18]([N:20]([CH:29]([CH3:31])[CH3:30])[C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[O:19])[C:10]3[CH:32]=[CH:33][CH:34]=[CH:35][C:9]2=3)[CH:5]=[CH:6][CH:7]=1.Br[CH2:37][C:38]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[N:40]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[N:39]=1>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([N:8]2[C:14](=[O:15])[CH:13]([CH2:37][C:38]3[C:46]4[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=4)[N:40]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[N:39]=3)[C:12](=[O:16])[N:11]([CH2:17][C:18]([N:20]([CH:29]([CH3:31])[CH3:30])[C:21]3[CH:22]=[CH:23][C:24]([O:27][CH3:28])=[CH:25][CH:26]=3)=[O:19])[C:10]3[CH:32]=[CH:33][CH:34]=[CH:35][C:9]2=3)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protectedHCID 67696368HCID 67696368, compound

Product 1

HCID 86753595HCID 86753595, compoundYield 63.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 260 mg (0.55 mmol) 2-[5-(3-Fluorophenyl)-2,4-dioxo-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Part A, in 4 mL DMF at 0° C. is added 1.3 mL (0.66 mmol, 1.2 equiv) KN(TMS)2 via syringe under N2. The reaction is allowed to warm to RT, and is stirred at RT for 20 min. The reaction is cooled to 0° C., and 200 mg (0.66 mmol, 1.2 equiv) 3-bromomethyl-1-tert-butoxycarbonyl-1H-indazole is added in one portion. The reaction is allowed to warm to RT, and after 20 min is concentrated. The reaction is then transferred to a separatory funnel containing water and ethyl acetate. The layers were separated, and the aqueous layer is extracted with ethyl acetate. The combined organics were dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel flash column chromatography (gradient 3:1-2:1 hexanes:ethyl acetate) to afford 248 mg of the title compound as a pale yellow foam: 1H NMR (CDCl3, 400 MHz) δ8.03 (d, br, 1H, J=8.4), 7.84 (d, 1H, J=8.0), 7.46 (t, 1H, J=7.7), 7.38-7.11 (m, 6H), 6.99-6.93 (m, 3H), 4.97 (m, 1H), 4.19 (d, 1H, J=16.6), 3.83 (s, 3H), 3.83 (m, 1H) 3.52 (dd, 1H, J=4.8, 16.6), 1.64 (s, 9H), 1.04 (d, 6H, J=6.7); low resolution MS (FAB)m/e 706 (MH+).

Workup

  1. temperatureThe reaction is cooled to 0° C.
  2. temperatureto warm to RT
  3. concentrationafter 20 min is concentrated
  4. customThe reaction is then transferred to a separatory funnel
  5. additioncontaining water and ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous layer is extracted with ethyl acetate
  8. dry with materialThe combined organics were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue is purified by silica gel flash column chromatography (gradient 3:1-2:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-46c95068582048678343415efdc99e11
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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