Ammonium Chloride → 8-{[(2-chloropyridin-3-yl)carbonyl]amino}-1-(4-ethynylphenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide

HRID 457334Notes

Reaction equation

HRID 457334 reaction equation
[NH2:1][C:2]1[CH:24]=[CH:23][C:5]2[CH2:6][CH2:7][C:8]3[C:9]([C:20]([NH2:22])=[O:21])=[N:10][N:11]([C:13]4[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=4)[C:12]=3[C:4]=2[CH:3]=1.[Si]([C:32]#[CH:33])(C(C)(C)C)(C)C.[Cl:34][C:35]1[N:42]=[CH:41][CH:40]=[CH:39][C:36]=1[CH2:37]Cl.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+].CN(C=[O:67])C.C(N(CC)CC)C>[Cu]I.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:34][C:35]1[C:36]([C:37]([NH:1][C:2]2[CH:24]=[CH:23][C:5]3[CH2:6][CH2:7][C:8]4[C:9]([C:20]([NH2:22])=[O:21])=[N:10][N:11]([C:13]5[CH:18]=[CH:17][C:16]([C:32]#[CH:33])=[CH:15][CH:14]=5)[C:12]=4[C:4]=3[CH:3]=2)=[O:67])=[CH:39][CH:40]=[CH:41][N:42]=1

Participants

9

Reactant 6

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 2757281(tert-Butyldimethylsilyl)acetyleneHCID 115283992-Chloro-3-chloromethyl-pyridineHCID 22056947triethylamine N,N-dimethylformamideHCID 222915188-amino-1-(4-bromophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide

Product 1

HCID 222915468-{[(2-chloropyridin-3-yl)carbonyl]amino}-1-(4-ethynylphenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

A stirred solution of 8-amino-1-(4-bromophenyl)-4,5-dihydro-1H-benzo[g]indazole-3-carboxamide (5.74 g, 15 mmol) and tert-butyldimethylsilylacetylene (2.31 g, 16.5 mmol) in DMF-triethylamine (20 mL-10 mL) was added CuI (285 mg, 1.5 mmol) and tetrakis(triphenylphosphine) palladium (870 mg, 0.75 mmol) and the resulted mixture was heated at 100° C. for 14 h before cooled to rt. The mixture was filtered through silica gel pad, washed with EtOAc, and concentrated. The crude material was taken into pyridine (30 mL), treated with 2-chloronicotinyl chloride (2.90 g, 16.5 mmol) at RT for 14 h. Tetrabutylammonium fluoride (25 mL of 1M THF solution, 25 mmol) was added at RT and stirred overnight. Aqueous ammonium chloride was added, the mixture extracted with EtOAc (5×30 mL). The organic portions were combined, dried over MgSO4, filtered, and separated by silica gel column (EtOAc). This gave product as a pale yellow solid (3.5 g, 49% over 3 steps). 1H NMR was consistent with its structure. CNH calculated for C26H18N5O2Cl(H2O)1.3: C(63.5%), H(4.2%), N(14.3%); found: C(63.6%), H(4.0%), N(14.3%).

Workup

  1. temperaturebefore cooled to rt
  2. filtrationThe mixture was filtered through silica gel pad
  3. washwashed with EtOAc
  4. concentrationconcentrated
  5. extractionthe mixture extracted with EtOAc (5×30 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customseparated by silica gel column (EtOAc)

Sources & evidence

ORD record
ord-d26e512405054e6fa896bac84b0d91fc
Source dataset
uspto-grants-2007_03
Patent number
US07186743B2

Reaction notes

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