3-(Bromomethyl)-1H-indazole, N1-BOC protected → HCID 67700777, compound

HRID 343180Notes

Reaction equation

HRID 343180 reaction equation
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[C:4](=[O:34])[CH2:3]1.Br[CH2:36][C:37]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[N:39]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[N:38]=1>CN(C=O)C.C1(C)C=CC=CC=1>[C:49]([O:48][C:46]([N:39]1[C:40]2[C:45](=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:37]([CH2:36][CH:3]2[C:2](=[O:1])[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]3[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=3)=[O:11])[C:7]3[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=3[N:5]([C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[C:4]2=[O:34])=[N:38]1)=[O:47])([CH3:52])([CH3:51])[CH3:50]

Participants

5

Reactant 2

HCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protectedHCID 67611178HCID 67611178, compound

Product 1

HCID 67700777HCID 67700777, compoundYield 62.7%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 597.8 mg (1.3 mmol) 2-(2,4-Dioxo-5-pyridin-3-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide, prepared as in Intermediate 48, in 15 mL DMF at 0° C. is added 3.13 mL (1.57 mmol, 1.2 equiv) of a 0.5M solution of KN(TMS)2 in toluene. The reaction is allowed to warm to RT over 20 min, then is cooled back to 0° C., and 445.4 mg (1.43 mmol, 1.1 equiv) of 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 in vacuo. The residue is taken up in water-ethyl acetate, and is poured into 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 in vacuo to afford an amber oil, which is purified by silica gel flash column chromatography to afford 561 mg of the title compound as a viscous, glassy oil: 1H NMR (CDCl3, 400 MHz) δ8.52 (d, br, 2H, J=18.8), 8.01 (d, 1H, J=8.4), 7.78 (m, 2H), 7.46 (t, 1H, J=20), 7.36-7.23 (m, 6H), 7.13 (m, 2H), 6.93 (m, 2H), 4.95 (m, 1H), 4.41 (d, br, 1H), 4.34 (dd, 1H, J=5.2, 8.4), 3.83 (s, 3H), 3.83 (dd, 1H), 3.55 (dd, 1H, J=5.1, 16.6), 1.64 (s, 9H), 1.03 (dd, 6H, J=2.0, 6.5); low resolution MS (FAB)m/e 689 (MH+).

Workup

  1. temperatureis cooled back to 0° C.
  2. temperatureto warm to RT
  3. concentration, and after 20 min is concentrated in vacuo
  4. additionis poured into 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 in vacuo
  11. customto afford an amber oil, which
  12. customis purified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-8b600f028d9047bca23a5fc80931da48
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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