3-(Bromomethyl)-1H-indazole, N1-BOC protected → HCID 67696995, compound

HRID 343182Notes

Reaction equation

HRID 343182 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:33]=[CH:32][N:31]=[CH:30][CH:29]=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>[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]=[CH:30][N:31]=[CH:32][CH:33]=3)[C:4]2=[O:34])=[N:38]1)=[O:47])([CH3:52])([CH3:51])[CH3:50]

Participants

4

Reactant 2

HCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protectedHCID 67575630HCID 67575630, compound

Product 1

HCID 67696995HCID 67696995, compoundYield 74.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of 437.3 mg 2-(2,4-Dioxo-5-pyridin-4-yl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl)-acetamide (0.95 mmol) in 10 mL DMF at 0° C. is added 2.09 mL (1.04 mmol, 1.1 equiv) of a 0.5M solution of KN(TMS)2. The reaction is allowed to warm to RT, then cooled back down to 0° C., and 325 mg (1.04 mmol, 1.1 equiv) 3-bromomethyl-1-tert-butoxycarbonyl-1H-indazole is then added in one portion. The reaction is allowed to warm to RT, and is stirred an additional 20 min. The reaction is then concentrated, diluted with H2O, and the aqueous layer is extracted with ethyl acetate (3×100 mL). The combined organics were dried (Na2SO4), filtered and concentrated. The residue is purified by silica gel flash column chromatography (gradient 1:1-2:1 ethyl acetate:hexanes) to afford 487 mg of the title compound as a pale yellow foam: 1H NMR (CDCl3, 400 MHz) δ8.58 (s, br, 2H), 8.01 (d, 1H, J=8.4), 7.93 (d, 1H, J=7.8), 7.47 (t, 1H, J=7.5), 7.38-7.26 (m, 4H) 7.26-7.11 (m, 4H), 6.94 (dd, 2H, J=8.7, 11.8), 4.94 (m, 1H), 4.39 (s, br, 1H), 4.32 (dd, 1H, J=4.9, 8.5), 4.16 (d, 1H, J=16.6), 3.83 (s, 3H), 3.80 (m, 1H), 3.52 (dd, 1H, J=5.1, 16.5), 1.62 (s, 9H), 1.03 (d, 6H, J=6.9); low resolution MS (FAB)m/e 689 (MH+).

Workup

  1. additionis then added in one portion
  2. temperatureto warm to RT
  3. concentrationThe reaction is then concentrated
  4. additiondiluted with H2O
  5. extractionthe aqueous layer is extracted with ethyl acetate (3×100 mL)
  6. dry with materialThe combined organics were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified by silica gel flash column chromatography (gradient 1:1-2:1 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-62301afef6034dc282b24f52dc4acab5
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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