3-(Bromomethyl)-1H-indazole, N1-BOC protected → 3-{6-[(benzyl-isopropyl-carbamoyl)-methyl]-8,9-difluoro-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl}-indazole-1-carboxylic acid tert-butyl ester

HRID 900104Notes

Reaction equation

HRID 900104 reaction equation
[CH2:1]([N:8]([CH:35]([CH3:37])[CH3:36])[C:9](=[O:34])[CH2:10][N:11]1[C:20](=[O:21])[CH2:19][C:18]2[N:14]([C:15]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[N:16][N:17]=2)[C:13]2[CH:28]=[C:29]([F:33])[C:30]([F:32])=[CH:31][C:12]1=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:38]([O:42][C:43]([N:45]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:47]([CH2:54]Br)=[N:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]>>[C:38]([O:42][C:43]([N:45]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:47]([CH2:54][CH:19]2[C:18]3[N:14]([C:15]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[N:16][N:17]=3)[C:13]3[CH:28]=[C:29]([F:33])[C:30]([F:32])=[CH:31][C:12]=3[N:11]([CH2:10][C:9](=[O:34])[N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:35]([CH3:37])[CH3:36])[C:20]2=[O:21])=[N:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]

Participants

3

Reactant 2

HCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protectedHCID 58957934N-benzyl-2-(8,9-difluoro-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-acetamide

Product 1

HCID 693127063-{6-[(benzyl-isopropyl-carbamoyl)-methyl]-8,9-difluoro-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl}-indazole-1-carboxylic acid tert-butyl esterYield 34.2%

Procedure

Following the procedure described in Example 3(A), Step A, N-benzyl-2-(8,9-difluoro-5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-N-isopropyl-acetamide (Preparation 9) (200 mg, 0.399 mmol) was alkylated with 3-bromomethyl-indazole-1-carboxylic acid tert-butyl ester (136 mg, 0.439 mmol). The reaction was diluted with a pH 6.8 buffer solution and the aqueous solution was extracted with EtOAc. The organic solution was washed with brine (4×), dried (Na2SO4), filtered and concentrated in vacuo. Purification by medium pressure chromatography eluting with a solvent gradient (CH2Cl2 to 30% MeOH in CH2Cl2) provided 100 mg of 3-{6-[(benzyl-isopropyl-carbamoyl)-methyl]-8,9-difluoro-5-oxo-1-phenyl-5,6-dihydro-4H-2,3,6,10b-tetraaza-benzo[e]azulen-4-ylmethyl}-indazole-1-carboxylic acid tert-butyl ester. MS 732.5 (M+1), 730.4 (M−1).

Workup

  1. extractionthe aqueous solution was extracted with EtOAc
  2. washThe organic solution was washed with brine (4×)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by medium pressure chromatography
  7. washeluting with a solvent gradient (CH2Cl2 to 30% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-45e28437ea264e68ba0bcaf58f2bb484
Source dataset
uspto-grants-2008_04
Patent number
US07358242B2

Reaction notes

Loading…