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Chemical Structure| 858629-06-8 Chemical Structure| 858629-06-8

Structure of 858629-06-8

Chemical Structure| 858629-06-8

5-Fluoro-3-iodo-1H-indazole

CAS No.: 858629-06-8

4.5 *For Research Use Only !

Cat. No.: A141691 Purity: 97%

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Product Details of [ 858629-06-8 ]

CAS No. :858629-06-8
Formula : C7H4FIN2
M.W : 262.02
SMILES Code : FC2=CC=C1[NH]N=C(C1=C2)I
MDL No. :MFCD06739145
InChI Key :CZUPBTJBMHZBTJ-UHFFFAOYSA-N
Pubchem ID :24728241

Safety of [ 858629-06-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 858629-06-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 48.77
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

28.68 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.38
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.34
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.73
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.73
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

3.42
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.52

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.54
Solubility 0.0748 mg/ml ; 0.000286 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.58
Solubility 0.687 mg/ml ; 0.00262 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-4.14
Solubility 0.0189 mg/ml ; 0.0000719 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.24 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<0.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

2.16

Application In Synthesis of [ 858629-06-8 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 858629-06-8 ]

[ 858629-06-8 ] Synthesis Path-Downstream   1~36

  • 1
  • [ 24424-99-5 ]
  • [ 858629-06-8 ]
  • [ 944904-49-8 ]
YieldReaction ConditionsOperation in experiment
With dmap; triethylamine; at 20℃; General procedure: 3-Iodo-1H-indazole (S1, 5.00 g, 19.5 mmol) was placed in a round-bottom flask and dissolved in tetrahydrofuran (100 mL). 4-Dimethylaminopyridine (0.24 g, 1.9 mmol, 0.1 equiv) was then added, followed by di-tert-butyl dicarbonate (5.4 mL, 24 mmol, 1.2 equiv). Triethylamine (5.4 mL, 39 mmol, 2.0 equiv) was slowly added to the clear, brown solution by syringe. The resulting solution was stirred at room temperature until it was complete as determined by TLC. The reaction was then diluted with water (75 mL) and ethyl acetate (50 mL). After separating the layers, the aqueous phase was extracted with additional ethyl acetate (3 × 50 mL). The combined organic layers were washed with brine (100 mL), then shaken over magnesium sulfate, filtered, and concentrated under reduced pressure to give the crude product. This material was purified by column chromatography over silica gel (hexanes/ethyl acetate: 100/0 to 90/10) to give the title compound as an orange solid (6.20 g, 93%).
  • 2
  • [ 348-26-5 ]
  • [ 858629-06-8 ]
YieldReaction ConditionsOperation in experiment
96.1% With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 0.5h; To a solution of 5-fluoro-1H-indazole (2.0 g, 14.0 mmol) in DIVIF (50 mL) was added ‘2 (7.46 g, 28.0 mmol) and KOH (2.4 g, 42 mmol), the mixture was stirred at room temperature for 0.5 hr. The reaction was monitored by TLC. After completion, the mixture was filtered, the filtrate was concentrated in vacuum to give a residue, which was purified by a silica gel column (PE/EA = 3/1) to afford 5-fluoro-3-iodo-1H-indazole (3.7 g, yield: 96.1%) as a white solid. ‘H NIVIR (400 IVIHz, DMSO-d6): ö = 13.64 (s, 1H), 7.63 (dd, J= 4.8, 4.4 Hz, 1H), 7.38-7.30 (m, 1H), 7.20 (dd, J=6.4,2.4Hz, 1H).
95.1% With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 1h; 5-Fluoro-1H-indazole (10.00 g, 73.46 mmol) was added into N,N-dimethylformamide(80 mL), then Iodine (28.0 g, 110 mmol) and potassium hydroxide (6.20 g, 110 mmol) wereadded. After addition, the mixture was reacted for 1 hour at room temperature. The reactionmixture was poured into aqueous sodium thiosulfate solution (300 mL, 5%). The resultingmixture was extracted with ethyl acetate (100 mL x 2). The combined organic layers werewashed with water (100 mL) and saturated brine (100 mL), dried over anhydrous sodium sulfate,and filtered. The filtrate was concentrated on a rotary evaporator to give a light yellow solid(18.3 g, 95.1 %)
87% With iodine; potassium hydroxide; In N,N-dimethyl-formamide; at 20℃; for 3h; General procedure: 3-Iodoindazoles were obtained by direct iodination of commercial indazoles by the method previously described by Bocchi [28] with slight modifications. A solution of 1H-indazole (3 g, 25.4 mmol), iodine (12.7 g, 50.03 mmol) and potassium hydroxide (5.34 g, 95.25 mmol)in DMF (7 mL) was stirred for 3 h at room temperature. The reaction was quenched by dilution with saturated solution of sodium bisulfite (150 mL) and a precipitated was formed. The precipitated was filtered over vacuum and washed with water (3 × 30 mL). The solid was left to dry at 30 C in a vacuum oven overnight obtaining 6.17 g of a pale yellow solid. Yield: 100%; m.p.: 136-138 C (lit.:[36] 134-136 C); IR (KBr) ν (cm-1): 3086 (NH); 424 (C-I). 1H-NMR δ (ppm): 13.50 (1H, s, H-1); 7.55(1H, d, J = 8.6 Hz, H-7); 7.45-7.40 (2H, m, H-6 and H-4); 7.19 (1H, dd, J = 7.5 Hz, H-5). 13C-NMR δ(ppm): 140.41; 127.22; 126.79; 121.23; 120.39; 110.51; 93.49; HRMS calculated for C7H5IN2: 243.9497,Found: 243.9499.3-Iodo-1H-indazole (1a). 3-Iodoindazoles were obtained by direct iodination of commercial indazoles by the method previously described by Bocchi [28] with slight modifications. A solution of 1H-indazole(3 g, 25.4 mmol), iodine (12.7 g, 50.03 mmol) and potassium hydroxide (5.34 g, 95.25 mmol) in DMF(7 mL) was stirred for 3 h at room temperature. The reaction was quenched by dilution with saturated solution of sodium bisulfite (150 mL) and a precipitated was formed. The precipitated was filtered over vacuum and washed with water (3 30 mL). The solid was left to dry at 30 C in a vacuum oven overnight obtaining 6.17 g of a pale yellow solid. Yield: 100%; m.p.: 136-138 C (lit.: [36] 134-136 C)
  • 3
  • [ 67-56-1 ]
  • [ 201230-82-2 ]
  • [ 858629-06-8 ]
  • [ 78155-73-4 ]
  • 4
  • [ 110-68-9 ]
  • [ 201230-82-2 ]
  • [ 858629-06-8 ]
  • [ 1352415-07-6 ]
YieldReaction ConditionsOperation in experiment
With iodine; sodium hydroxide; In methanol; at 20℃; for 48h; General procedure: 3-lodo-1H-indazole Iodine (5.8 g, 22.9 mmol) was added in portions over approximately 20 min to a solution of indazole (2.5 g, 21.7 mmol) in methanol (63 ml) and 2N sodium hydroxide solution (65 ml). The mixture remained colourless and a white precipitate slowly formed. The mixture was stirred at room temperature 48 h. The mixture was cooled in an ice-bath and 7.5 ml of concentrated hydrochloric acid was slowly added. The mixture was further acidified with 2N hydrochloric acid. 20% w/v Sodium thiosulfate pentahydrate solution was added until the iodine colour disappeared. The precipitate was filtered, washed with water and dried in the oven at 50 ºC to constant weight. The solid was taken up in methanol, filtered and the filtrated was evaporated under reduced pressure to give 5.0 g (20.6 mmol, 95%) of the title compound as a white solid. Purity 100%.1H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.43-7.59 (m, 3H), 7.21-7.26 (m, 1H).UPLC/MS (3 min) retention time 1.56 min.LRMS: m/z 245 (M+1).
With iodine; sodium hydroxide; In methanol; at 20℃; for 48h; General procedure: Iodine (5.8 g, 22.9 mmol) was added in portions over approximately 20 min to a solution of indazole (2.5 g, 21 .7 mmol) in methanol (63 ml) and 2N sodium hydroxide solution (65 ml). The mixture remained colourless and a white precipitate slowly formed. The mixture was stirred at room temperature 48 h. The mixture was cooled in an ice-bath and 7.5 ml of concentrated hydrochloric acid was slowly added. The mixture was further acidified with 2N hydrochloric acid. 20% w/v Sodium thiosulfate pentahydrate solution was added until the iodine colour disappeared. The precipitate was filtered, washed with water and dried in the oven at 50 C to constant weight. The solid was taken up in methanol, filtered and the filtrated was evaporated under reduced pressure to give 5.0 g (20.6 mmol, 95%) of the title compound as a white solid. Purity 100%. 1 H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.43-7.59 (m, 3H), 7.21 -7.26 (m, 1 H). UPLC/MS (3 min) retention time 1 .56 min. LRMS: m/z 245 (M+1 ).
  • 6
  • [ 858629-06-8 ]
  • C16H13FN2O2 [ No CAS ]
  • 7
  • [ 858629-06-8 ]
  • [ 57614-63-8 ]
  • 8
  • [ 353-83-3 ]
  • [ 858629-06-8 ]
  • [ 1613515-95-9 ]
YieldReaction ConditionsOperation in experiment
46% With potassium carbonate; In acetonitrile;Reflux; General procedure: Potassium carbonate (791 mg, 5.7 mmol) was added to a solution of 3-iodoindazole (700 mg, 2.9 mmol) and 2-chloroethyl methyl ether (406 mg, 4.3 mmol) in ACN (20 mL) at rt. The reaction was heated to reflux overnight, and then was filtered and concentrated. The residue was purified by silica gel chromatography (15%-50% EtOAc/hexanes) to give 530 mg (63%) of the title compound as a light yellow oil. The title compound was prepared in 46% yield from 5-fluoro-3-iodo-indazole and 1,1,1-trifluoro-2-iodoethane according to the general procedure for Preparation 10A. The minor isomer was not isolated or characterized. 1H NMR (400 MHz, CDCl3): δ 4.91-4.97 (2H, m), 7.17 (1H, dd, J=2.0, 8.0 Hz), 7.30 (1H, td, J=2.0, 8.4 Hz), 7.38 (1H, dd, J=3.6, 9.2 Hz).
  • 9
  • [ 858629-06-8 ]
  • [ 100-39-0 ]
  • [ 1613515-96-0 ]
YieldReaction ConditionsOperation in experiment
75% With potassium carbonate; In acetonitrile;Reflux; General procedure: Potassium carbonate (791 mg, 5.7 mmol) was added to a solution of 3-iodoindazole (700 mg, 2.9 mmol) and 2-chloroethyl methyl ether (406 mg, 4.3 mmol) in ACN (20 mL) at rt. The reaction was heated to reflux overnight, and then was filtered and concentrated. The residue was purified by silica gel chromatography (15%-50% EtOAc/hexanes) to give 530 mg (63%) of the title compound as a light yellow oil. The title compound was prepared in 75% yield from 5-fluoro-3-iodo-indazole and benzyl bromide according to the general procedure for Preparation 10A. The minor isomer was not isolated or characterized. 1H NMR (400 MHz, CDCl3): δ 5.59 (2H, s), 7.11-7.21 (5H, m), 7.23-7.31 (3H, m).
  • 10
  • [ 3814-30-0 ]
  • [ 858629-06-8 ]
  • [ 1613516-08-7 ]
  • [ 1613516-09-8 ]
YieldReaction ConditionsOperation in experiment
72%; 18% With potassium carbonate; In acetonitrile;Reflux; General procedure: Potassium carbonate (791 mg, 5.7 mmol) was added to a solution of 3-iodoindazole (700 mg, 2.9 mmol) and 2-chloroethyl methyl ether (406 mg, 4.3 mmol) in ACN (20 mL) at rt. The reaction was heated to reflux overnight, and then was filtered and concentrated. The residue was purified by silica gel chromatography (15%-50% EtOAc/hexanes) to give 530 mg (63%) of the title compound as a light yellow oil. The title compounds were prepared from 5-fluoro-3-iodo-indazole and (bromomethyl)cyclopentane according to the procedure for Preparation 10A. [0365] 1-(cyclopentylmethyl)-<strong>[858629-06-8]5-fluoro-3-iodo-1H-indazole</strong> (72%) was isolated as the major isomer eluting first. 1H NMR (400 MHz, CDCl3): δ 1.25-1.32 (2H, m), 1.50-1.65 (6H, m), 2.48-2.56 (1H, m), 4.27 (2H, d, J=7.5 Hz), 7.09 (1H, dd, J=8.3, 2.3 Hz), 7.18 (1H, td, J=8.9, 2.4 Hz), 7.32 (1H, dd, J=9.1, 4.0 Hz). [M+H] calc'd for C13H14FIN2, 345. found 345. [0366] 2-(cyclopentylmethyl)-5-fluoro-3-iodo-2H-indazole (18%) was isolated as the minor isomer eluting second. 1H NMR (400 MHz, CDCl3): δ 1.33-1.42 (2H, m), 1.56-1.73 (6H, m), 2.62-2.70 (1H, m), 4.41 (2H, d, J=7.6 Hz), 7.00 (1H, dd, J=8.8, 2.4 Hz), 7.09 (1H, td, J=9.2, 2.4 Hz), 7.65 (1H, dd, J=9.3, 4.5 Hz). [M+H] calc'd for C13H14FIN2, 345. found 345.
  • 11
  • [ 858629-06-8 ]
  • [ 107-06-2 ]
  • [ 1613516-88-3 ]
YieldReaction ConditionsOperation in experiment
67% With potassium carbonate; In acetonitrile;Reflux; To a solution of 5-fluoro-3-iodo-indazole (3.0 g, 11.5 mmol) and 1,2-dichloroethane (5.7 g, 57.3 mmol) in ACN (50 mL) was added K2CO3 (3.2 g, 22.9 mmol) at rt. The reaction was stirred overnight at reflux. The reaction mixture was filtered and concentrated in vacuo. Purification by silica gel chromatography (30:1:5 hexanes/EtOAc/DCM) gave 2.5 g (67%) of the title compound as a yellow solid. 1H NMR (300 MHz, CDCl3): δ 3.97 (2H, t, J=6.0 Hz), 4.69 (2H, t, J=6.0 Hz), 7.13 (1H, dd, J=1.8, 7.8 Hz), 7.22-7.29 (1H, m), 7.42 (1H, dd, J=3.9, 9.3 Hz).
  • 12
  • [ 858629-06-8 ]
  • [ 1613515-93-7 ]
  • 13
  • [ 858629-06-8 ]
  • [ 1613516-39-4 ]
  • 14
  • [ 858629-06-8 ]
  • [ 1613516-40-7 ]
  • 15
  • [ 858629-06-8 ]
  • [ 1613516-89-4 ]
  • 16
  • [ 858629-06-8 ]
  • [ 1613515-42-6 ]
  • 17
  • [ 858629-06-8 ]
  • [ 1613516-90-7 ]
  • 18
  • [ 137-43-9 ]
  • [ 858629-06-8 ]
  • [ 1613516-06-5 ]
YieldReaction ConditionsOperation in experiment
71% With potassium carbonate; In acetonitrile;Reflux; General procedure: Potassium carbonate (1.1 g, 8.2 mmol) was added to a solution of 3-iodoindazole (1.0 g, 4.1 mmol) and bis(2-chloroethyl)ether (1.5 g, 10.3 mmol) in ACN (20 mL) at rt. The reaction was heated to reflux overnight, and the filtered and concentrated. The residue was purified by silica gel chromatography to give 800 mg (56%) of the title compound as a yellow oil. The title compound was prepared in 71% yield from 5-fluoro-3-iodo-indazole and bromocyclopentane according to the procedure for Preparation 11A. The minor isomer was not isolated cleanly. 1H NMR (400 MHz, CDCl3): δ 1.69-1.76 (2H, m), 1.92-1.98 (2H, m), 2.12-2.18 (4H, m), 4.87-4.95 (1H, m), 7.08 (1H, dd, J=8.2, 2.3 Hz), 7.17 (1H, td, J=8.9, 2.4 Hz), 7.35 (1H, dd, J=9.1, 4.0 Hz). [M+H] calc'd for C12H12FIN2, 331. found 331..
  • 19
  • [ 858629-06-8 ]
  • [ 7250-67-1 ]
  • [ 1613516-50-9 ]
YieldReaction ConditionsOperation in experiment
88% With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 68℃; for 3h; Potassium carbonate (950 mg, 6.9 mmol) and potassium iodide (380 mg, 2.3 mmol) were added to a solution of 5-fluoro-3-iodo-indazole (600 mg, 2.3 mmol) and 1-(2-chloroethyl)pyrrolidine hydrochloride (779 mg, 4.6 mmol) in DMF (15 mL) at rt. The reaction was heated to 68 C. for 3 h and then allowed to cool to rt. The reaction was filtered, washing with MeOH, and the solution was concentrated. Purification by silica gel chromatography (10% MeOH/DCM) gave 720 mg (88%) of the title compound as a clear oil. This material contained a slight (minor isomer) impurity. 1H NMR (400 MHz, CDCl3): δ 1.76-1.81 (4H, m), 2.58-2.64 (4H, m), 3.05 (2H, t, J=7.3 Hz), 4.56 (2H, t, J=7.3 Hz), 7.10 (1H, dd, J=8.2, 4.7 Hz), 7.21 (1H, td, J=8.9, 2.3 Hz), 7.42 (1H, dd, J=9.1, 4.0 Hz). [M+H] calc'd for C13H15FIN3, 360. found, 360.
  • 20
  • [ 2566-44-1 ]
  • [ 858629-06-8 ]
  • [ 1613516-11-2 ]
  • [ 1613516-12-3 ]
YieldReaction ConditionsOperation in experiment
59%; 33% With di-tert-butyl dicarbonate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 16h; 5-Fluoro-3-iodo-indazole (524 mg, 2.0 mmol), 2-cylcopropylethanol (344 mg, 4.0 mmol), and triphenylphosphine (1.05 g, 4.0 mmol) were combined in dry THF (40 mL). Di-tert-butyl azodicarboxylate (921 mg, 4.0 mmol) was added, and the reaction was stirred for 16 h at rt. The solution was concentrated and purified by silica gel chromatography (0% to 20% EtOAc/hexanes) to give two product isomers: 1-(cyclopropylethyl)-<strong>[858629-06-8]5-fluoro-3-iodo-1H-indazole</strong> (390 mg, 59%) was isolated as the major isomer eluting first. 1H NMR (400 MHz, CDCl3): δ 0.03-0.01 (2H, m), 0.29-0.41 (2H, m), 0.55-0.62 (1H, m), 1.76-1.82 (2H, m), 4.45 (2H, t, J=7.0 Hz), 7.09 (1H, dd, J=8.4, 2.3 Hz), 7.19 (1H, td, J=8.9, 2.4 Hz), 7.35 (1H, dd, J=9.1, 4.0 Hz). [M+H] calc'd for C12H12FIN2, 331. found 331. 2-(cyclopropylethyl)-5-fluoro-3-iodo-2H-indazole (216 mg, 33%) was isolated as the minor isomer eluting second. 1H NMR (400 MHz, CDCl3): δ 0.03-0.01 (2H, m), 0.29-0.42 (2H, m), 0.61-0.69 (1H, m), 1.79-1.85 (2H, m), 4.53 (2H, t, J=7.2 Hz), 6.95 (1H, dd, J=8.7, 2.4 Hz), 7.06 (1H, td, J=9.2, 2.4 Hz), 7.59 (1H, dd, J=9.3, 4.55 Hz). [M+H] calc'd for C12H12FIN2, 331. found 331.
  • 21
  • [ 36865-41-5 ]
  • [ 858629-06-8 ]
  • [ 1613515-76-6 ]
  • [ 1613515-77-7 ]
YieldReaction ConditionsOperation in experiment
47%; 17% General procedure: 5-Chloro-3-iodo-indazole (1.0 g, 3.6 mmol) was stirred in DMF (8 mL) at 0 C. under N2. NaH (60%, 159 mg, 3.96 mmol) was added, and the reaction stirred 45 min. Iodomethane (260 μL, 4.14 mmol) was added, and the reaction stirred 45 min while warming to rt. The solution was quenched with MeOH and concentrated. Purification by silica gel chromatography (10%-40% EtOAc/hexanes gave two isomers: _The title compounds were prepared from 5-fluoro-3-iodo-indazole and 1-bromo-3-methoxypropane according to the procedure for Preparation 4A and 4B. [0275] 5-fluoro-3-iodo-1-(methoxypropyl)-1H-indazole (47%) was isolated as the major isomer eluting first. 1H NMR (400 MHz, CDCl3): δ 2.12-2.19 (2H, m), 3.23-3.33 (5H, m), 4.48 (2H, t, J=6.6 Hz), 7.09 (1H, dd, J=8.3, 2.3 Hz), 7.18 (1H, td, J=8.9, 2.4 Hz), 7.38 (1H, dd, J=9.1, 4.0 Hz). [M+H] calc'd for C11H12FIN2O, 335. found 335. [0276] 5-fluoro-3-iodo-2-(methoxypropyl)-2H-indazole (17%) was isolated as the minor isomer eluting second. 1H NMR (400 MHz, CDCl3): δ 2.21-2.28 (2H, m), 3.34-3.39 (5H, m), 4.60 (2H, t, J=7.0 Hz), 7.00 (1H, dd, J=8.7, 2.4 Hz), 7.10 (1H, td, J=9.1, 2.4 Hz), 7.64 (1H, dd, J=9.2, 4.5 Hz). [M+H] calc'd for C11H12FIN2O, 335. found 335.
  • 22
  • [ 111-24-0 ]
  • [ 858629-06-8 ]
  • [ 1613515-91-5 ]
  • [ 1613515-92-6 ]
YieldReaction ConditionsOperation in experiment
57%; 14% With potassium carbonate; In acetonitrile;Reflux; General procedure: Potassium carbonate (1.1 g, 8.2 mmol) was added to a solution of 3-iodoindazole (1.0 g, 4.1 mmol) and bis(2-chloroethyl)ether (1.5 g, 10.3 mmol) in ACN (20 mL) at rt. The reaction was heated to reflux overnight, and the filtered and concentrated. The residue was purified by silica gel chromatography to give 800 mg (56%) of the title compound as a yellow oil. The minor isomer was not isolated or characterized.The title compounds were prepared from 5-fluoro-3-iodo-indazole an 1,5-dibromopentane according to the general procedure for Preparation 11A. [0315] 1-(5-bromopentyl)-<strong>[858629-06-8]5-fluoro-3-iodo-1H-indazole</strong> (57%) was isolated as the major isomer eluting first. 1H NMR (400 MHz, CDCl3): δ 1.45-1.51 (2H, m), 1.84-1.99 (4H, m), 3.37 (2H, t, J=6.7 Hz), 4.38 (2H, t, J=7.1 Hz), 7.12 (1H, dd, J=8.3, 2.3 Hz), 7.21 (1H, td, J=8.9, 2.4 Hz), 7.33 (1H, dd, J=9.2, 4.0 Hz). [M+H] calc'd for C12H13BrFIN2, 412. found 412. [0316] 2-(5-bromopentyl)-5-fluoro-3-iodo-2H-indazole (14%) was isolated as the minor isomer eluting second. 1H NMR (400 MHz, CDCl3): δ 1.48-1.56 (2H, m), 1.88-2.06 (4H, m), 3.40 (2H, t, J=6.7 Hz), 4.51 (2H, t, J=7.2 Hz), 7.00 (1H, dd, J=8.6, 2.4 Hz), 7.11 (1H, td, J=9.2, 2.4 Hz), 7.64 (1H, dd, J=9.2, 4.5 Hz). [M+H] calc'd for C12H13BrFIN2, 412. found 412.
  • 23
  • [ 21156-84-3 ]
  • [ 858629-06-8 ]
  • [ 1613516-27-0 ]
YieldReaction ConditionsOperation in experiment
30% With di-tert-butyl dicarbonate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 16h; General procedure: 5-Fluoro-3-iodo-indazole (524 mg, 2.0 mmol), 2-cylcopropylethanol (344 mg, 4.0 mmol), and triphenylphosphine (1.05 g, 4.0 mmol) were combined in dry THF (40 mL). Di-tert-butyl azodicarboxylate (921 mg, 4.0 mmol) was added, and the reaction was stirred for 16 h at rt. The solution was concentrated and purified by silica gel chromatography (0% to 20% EtOAc/hexanes) to give two product isomers: 1-(cyclopropylethyl)-<strong>[858629-06-8]5-fluoro-3-iodo-1H-indazole</strong> (390 mg, 59%) was isolated as the major isomer eluting first. The title compound was prepared from 5-fluoro-3-iodo-indazole and 1-methyl-4-(hydroxyethyl)piperidine in 30% yield according to the general procedure for Preparation 31A. The minor isomer was not isolated or characterized. 1H NMR (300 MHz, CDCl3): δ 1.23-1.42 (3H, m), 1.72-1.76 (2H, m), 1.84-1.91 (4H, m), 2.56 (3H, s), 2.82-2.86 (2H, m), 4.41 (2H, t, J=7.8 Hz), 7.13 (1H, dd, J=2.4, 8.4 Hz), 7.22 (1H, td, J=2.4, 8.7 Hz), 7.33 (1H, dd, J=3.9, 9.0 Hz).
  • 24
  • [ 3240-94-6 ]
  • [ 858629-06-8 ]
  • [ 1613516-62-3 ]
YieldReaction ConditionsOperation in experiment
70% With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 68℃; for 3h; General procedure: Potassium carbonate (950 mg, 6.9 mmol) and potassium iodide (380 mg, 2.3 mmol) were added to a solution of 5-fluoro-3-iodo-indazole (600 mg, 2.3 mmol) and 1-(2-chloroethyl)pyrrolidine hydrochloride (779 mg, 4.6 mmol) in DMF (15 mL) at rt. The reaction was heated to 68 C. for 3 h and then allowed to cool to rt. The reaction was filtered, washing with MeOH, and the solution was concentrated. Purification by silica gel chromatography (10% MeOH/DCM) gave 720 mg (88%) of the title compound as a clear oil. This material contained a slight (minor isomer) impurity. The title compound was prepared in 70% yield from 5-fluoro-3-iodo-indazole and 4-(2-chloroethyl)morpholine according to the general procedure for Preparation 50A. 1H NMR (400 MHz, CDCl3): δ 2.46-2.52 (4H, m), 2.82-2.89 (2H, m), 3.57-3.67 (4H, m), 4.49 (2H, t, J=6.7 Hz), 7.11 (1H, dd, J=8.2, 2.3 Hz), 7.21 (1H, td, J=8.9, 2.3 Hz), 7.36 (1H, dd, J=9.0, 3.9 Hz). [M+H] calc'd for C13H15FIN3O, 376. found, 376.
  • 25
  • [ 858629-06-8 ]
  • [ 89031-82-3 ]
  • [ 1613516-29-2 ]
YieldReaction ConditionsOperation in experiment
79% With di-tert-butyl dicarbonate; triphenylphosphine; In tetrahydrofuran; at 20℃; for 16h; General procedure: 5-Fluoro-3-iodo-indazole (524 mg, 2.0 mmol), 2-cylcopropylethanol (344 mg, 4.0 mmol), and triphenylphosphine (1.05 g, 4.0 mmol) were combined in dry THF (40 mL). Di-tert-butyl azodicarboxylate (921 mg, 4.0 mmol) was added, and the reaction was stirred for 16 h at rt. The solution was concentrated and purified by silica gel chromatography (0% to 20% EtOAc/hexanes) to give two product isomers: 1-(cyclopropylethyl)-<strong>[858629-06-8]5-fluoro-3-iodo-1H-indazole</strong> (390 mg, 59%) was isolated as the major isomer eluting first. The title compound was prepared from 5-fluoro-3-iodo-indazole and (3-chloropropoxy)tert-butyldimethylsilane (Org. Lett., 2000, 3473) in 79% yield according to the general procedure for Preparation 31A. The minor isomer was not isolated or characterized. 1H NMR (400 MHz, CDCl3): δ 0.06 (6H, s), 0.89 (9H, s), 2.07-2.13 (2H, m), 3.55 (2H, t, J=6.0 Hz), 4.49 (2H, t, J=6.0 Hz), 7.10 (1H, dd, J=2.4, 8.4 Hz), 7.18 (1H, td, J=2.4, 8.8 Hz), 7.40 (1H, dd, J=4.0, 8.8 Hz).
  • 26
  • [ 858629-06-8 ]
  • [ 24067-17-2 ]
  • 5-fluoro-3-(4-nitrophenyl)-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
95.4% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 80℃; To a solution of <strong>[858629-06-8]5-fluoro-3-iodo-1H-indazole</strong> (2.0 g, 7.6 mmol) in dioxane (40 mL) and H20 (10 mL) was added 4-nitrophenylboronic acid (1.89 g, 11.4 mmol) and K2C03 (2.09 g, 15.2 mmol), Pd(dppf)C12 (555.56 mg, 0.76 mmol), the mixture was stirred at 80 C overnight. The reaction was monitored by TLC. After completion, the mixture was filtered, the filtrate was concentrated in vacuum to give a residue, which was purified by a silica gel column (PE/EA = 3/1) to afford 5-fluoro-3-(4-nitro-phenyl)-1H-indazole (1.87 g, yield: 95.4%) as a yellow solid. ‘HNIVIR (400 IVIHz, DMSO-d6): ö = 14.06 (s, 1H), 8.41-8.28 (m, 4H), 7.99 (dd,J 7.2, 2.0 Hz, 1H), 7.73 (dd, J 4.4, 4.8 Hz, 1H), 7.41-7.33 (m, 1H)
  • 27
  • [ 858629-06-8 ]
  • 5-fluoro-1-methyl-3-(4-nitrophenyl)-1H-indazole [ No CAS ]
  • 28
  • [ 858629-06-8 ]
  • 4-(5-fluoro-1-methyl-1H-indazol-3-yl)phenylamine [ No CAS ]
  • 29
  • [ 858629-06-8 ]
  • [4-(5-fluoro-1-methyl-1H-indazol-3-yl)phenyl]carbamic acid phenyl ester [ No CAS ]
  • 30
  • [ 858629-06-8 ]
  • 1-[4-(5-fluoro-1-methyl-1H-indazol-3-yl)phenyl]-3-pyridin-4-ylmethylurea [ No CAS ]
  • 31
  • [ 858629-06-8 ]
  • C9H17BO2 [ No CAS ]
  • 5-fluoro-3-vinyl-1H-indazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
47% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 120℃; for 0.666667h;Inert atmosphere; Microwave irradiation; General procedure: Method a: A mixture of 3-iodoindazole (0.2 g, 0.82 mmol), 2 equivalents ofvinyl boronic acid pinacol ester (0.27 mL, 1.62 mmol), tetrakis triphenylphosphine palladium (52 mg,0.045 mmol), an aqueous solution of sodium carbonate 2N (2 mL) and 1,4-dioxane (7 mL), were placedin a microwave glass tube and purged with nitrogen. The closed tube was placed under microwaveirradiation to 120 C for 40 min. After irradiation was completed, the reaction was stopped by dilutionusing 50 mL of brine. The organic layer was extracted with ethylacetate (3 × 45 mL) and the combinedorganic layers were dried over anhydrous sodium sulfate. Removal of the solvent under vacuumafforded a brown oil crude residue. The oil was purified by column chromatography on silica gel(hexane/ethylacetate 7:3) to yield 89 mg of white crystalline plates. Yield: 75%.
  • 32
  • [ 858629-06-8 ]
  • 5-fluoro-1-(2-fluorobenzyl)-1H-indazole-3-carbonitrile [ No CAS ]
  • 33
  • [ 858629-06-8 ]
  • 5-fluoro-1-(2-fluorobenzyl)-1H-indazole-3-carboximidamide [ No CAS ]
  • 34
  • [ 858629-06-8 ]
  • 2-(5-fluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)-5-(phenyldiazenyl)pyrimidine-4,6-diamine [ No CAS ]
  • 35
  • [ 858629-06-8 ]
  • 2-(5-fluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)pyrimidine-4,5,6-triamine [ No CAS ]
  • 36
  • [ 858629-06-8 ]
  • methyl (4,6-diamino-2-(5-fluoro-1-(2-fluorobenzyl)-1H-indazol-3-yl)pyrimidin-5-yl)carbamate [ No CAS ]
 

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