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Chemical Structure| 1798-85-2 Chemical Structure| 1798-85-2

Structure of 1798-85-2

Chemical Structure| 1798-85-2

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Product Details of [ 1798-85-2 ]

CAS No. :1798-85-2
Formula : C9H9Br
M.W : 197.07
SMILES Code : BrC1=CC(=CC=C1)C1CC1
MDL No. :MFCD01070823
InChI Key :BCBNVQYWODLZSI-UHFFFAOYSA-N
Pubchem ID :3282672

Safety of [ 1798-85-2 ]

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

Computational Chemistry of [ 1798-85-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.33
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 46.61
TPSA ?

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

0.0 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.56
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

3.96
Log Po/w (WLOGP)?

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

3.26
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.

3.59
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

3.64
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.4

Water Solubility

Log S (ESOL):?

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

-3.93
Solubility 0.0229 mg/ml ; 0.000116 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.

-3.66
Solubility 0.0431 mg/ml ; 0.000219 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

-3.85
Solubility 0.0276 mg/ml ; 0.00014 mol/l
Class?

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

Soluble

Pharmacokinetics

GI absorption?

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

Low
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

Yes
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.

-4.69 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

2.0
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

0.0 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<2.0
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)

1.45

Application In Synthesis of [ 1798-85-2 ]

* 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 [ 1798-85-2 ]

[ 1798-85-2 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 124-38-9 ]
  • [ 1798-85-2 ]
  • [ 1129-06-2 ]
YieldReaction ConditionsOperation in experiment
43% 1.0 M Diethyl zinc in hexanes (27.3 ml, 27.3 mmol) was added to a solution of 2,4, 6- [TRICHLOROPHENOL] (5.4g, 27.3 mmol) in dichloromethane (100 ml) at-40C. After stirring for 15 minutes, diiodo-methane (2.2 mL, 27.3 mmol) was added at-40C and stirred for an additional 15 minutes. 1-Bromo-3-vinyl-benzene (2.5 g, 13.7 mmol) was then added to the reaction mixture, allowed to warm to room temperature, and left stirring overnight. The reaction mixture was diluted with dichloromethane, washed with 1N [HC1] (2X), saturated sodium bicarbonate (2X), saturated sodium sulfite, 1N sodium hydroxide, and saturated brine, dried over magnesium sulfate, filtered and concentrated. GC-MS revealed that the reaction mixture contained [L-BROMO-3-CYCLOPROPYL-BENZENE] and 1-bromo-3-vinyl-benzene. To remove the bromo-3-vinyl-benzene, the crude mixture was reacted with potassium permanganate. A solution of potassium permanganate/water (1.5 g/20 mL) was added drop-wise to a solution of the crude mixture [(-3.] 5 g) in THF (40 mL) at [0C] and then allowed to warm to room temperature. After 1 hour, the reaction was diluted with diethyl ether, washed with water and saturated brine, dried over anhydrous sodium sulfate filtered and concentrated. Purication by flash column chromatography eluted with 100 hexanes afforded [1-BROMO-3-CYCLOPROPYL-BENZENE] (2.20g, [81%).] 1.6 M n-Butyllithium in hexanes (3.2 mL, 5.1 mmol) was added drop-wise to a solution of [L-BROMO-3-CYCLOPROPYL-BENZENE] [AT-78C] and stirred for 1 hour. This reaction mixture was then transferred via canula to a 250 mL round bottom flask equipped with a stirrer bar approximately [1/4 FULL] of solid carbon dioxide and stirred and for 1 hour. The reaction mixture was concentrated and then the residue was diluted with water. The aqueous layer was washed with dichloromethane [(3X),] acidified with 1 N [HC1] to [PH-2,] and extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford 3-cyclopropyl-benzoic (356 mg, 43%, white [SOLID). IH NMR (DMSO), 6] (ppm): 12.90 (bs, 1H), 7.71 (d, 1H), 7.64 (s, 1H), 7.34 (m, 2H), 2.01 (m, 1H), 0.99 (m, 2H), 0.70 (m, 2H).
  • 2
  • [ 1798-85-2 ]
  • [ 544-92-3 ]
  • [ 54134-94-0 ]
  • 3
  • [ 1798-85-2 ]
  • [ 544-92-3 ]
  • [ 1129-06-2 ]
  • 4
  • [ 1798-85-2 ]
  • [ 75-07-0 ]
  • [ 40641-99-4 ]
  • 5
  • [ 1798-85-2 ]
  • [ 67-64-1 ]
  • [ 19936-13-1 ]
  • 6
  • β-<N,N-dimethylamino>-3-bromopropiophenone hydrochloride [ No CAS ]
  • [ 1798-85-2 ]
  • 7
  • 4-Brom-2-cyclopropylanilin-hydrochlorid [ No CAS ]
  • [ 1798-85-2 ]
  • 9
  • [ 1798-85-2 ]
  • [ 1206522-33-9 ]
YieldReaction ConditionsOperation in experiment
<strong>[1798-85-2]Bromo-3-cyclopropyl-benzene</strong> (1.0 g, 5.1 mmol) [prep.: J. Org. Chem. vol. 41, 2262-6 (1976)] was dissolved in dry THF/diethyl ether (1:1, 30 ml) under an argon atmosphere and cooled to -78 C. BuLi (1.6 M in hexanes, 3.2 ml, 5.1 mmol) was added dropwise and the reaction mixture was further stirred at low temperature for 15 min. This reaction mixture was added via cannula to a SO2 gas saturated solution of diethyl ether (20 ml) precooled to -78 C. The reaction mixture was stirred overnight at room temperature and concentrated under reduced pressure. The crude intermediate was suspended in n-hexane (4A sieves dried, 20 ml) and chilled (ice-water). A solution of sulfuryl chloride (0.3 ml, 3.6 mmol) in dry hexane (8 ml) was added dropwise to the stirred suspension and then the cold bath was removed. After 90 min at room temperature the reaction mixture was filtered (Speedex pad) and the filtrate was concentrated under reduced pressure to yield a yellow oil: 0.6 g, (67%) GC-MS: M=216.
  • 10
  • [ 1798-85-2 ]
  • [ 1017264-51-5 ]
YieldReaction ConditionsOperation in experiment
To a solution of 0.985 g <strong>[1798-85-2]1-bromo-3-cyclopropyl-benzene</strong> in 5 ml tetrahydrofuran was drop wise added at -78 C. 2.81 ml of a 1.6M solution of n-butyllithium in hexane. The mixture was stirred at -78 C. for 1.5 h. To the resulting suspension was added drop wise an excess (ca 1.5 ml) of sulfur dioxide (condensed with a dry ice cooling trap) and the mixture was allowed to taw to room temperature. The resulting suspension was stirred at room temperature for 45 min. The solid was collected by filtration washed with heptane and dried under high vacuum to constant weight to yield 0.67 g of a light yellow solid. This material was dissolved in 5.0 ml water and 0.467 g sodium acetate and 0.604 g hydroxylamine-O-sulfonic acid was added. The reaction mixture was stirred for 30 min at ambient temperature whereby a precipitate formed. The solid was collected and washed with water and dried to constant weight to yield 0.44 g of the title compound as a light yellow solid melting at 71.5-72.9 C.
  • 12
  • [ 2142-63-4 ]
  • [ 1798-85-2 ]
YieldReaction ConditionsOperation in experiment
34 g of 3-cyclopropyl bromobenzene was synthesized from 50 g of 3-bromoacetophenone by a method described in J. Org. Chem., 41, 2263 (1976), and 2 9 of this product was used to prepare 520 mg of the title compound as a white solid by the method described in Production Example 427.1H-NMR (DMSO-d6) delta: 0.63(m, 2H), 0.90(m, 2H), 1.83(m, 1H), 3.20(m, 4H), 3.30(m, 4H), 6.54(d, J=8.0Hz, 1H), 6.68(s, 1H), 6.72(d, J=8.0Hz, 1H), 7.10(t, J=8.0Hz, 1H)
  • 13
  • [ 1798-85-2 ]
  • [ 40642-01-1 ]
  • 14
  • [ 1798-85-2 ]
  • 1-(3-cyclopropylphenyl)piperazine di-trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Production Example 434 1-(3-Cyclopropylphenyl)piperazine di-trifluoroacetate 34 g of <strong>[1798-85-2]3-cyclopropyl bromobenzene</strong> was synthesised from 50 g of 3-bromoacetophenone by a method described in J. Org. Chem., 41, 2263 (1976), and 2 9 of this product was used to prepare 520 mg of the title compound as a white solid by the method described in Production Example 427.1H-NMR (DMSO-d6) delta: 0.63(m, 2H), 0.90(m, 2H), 1.83(m, 1H), 3.20(m, 4H), 3.30(m, 4H), 6.54(d, J=8.0Hz, 1H), 6.68(s, 1H), 6.72(d, J=8.0Hz, 1H), 7.10(t, J=8.0Hz, 1H)
  • 15
  • [ 75-11-6 ]
  • [ 2039-86-3 ]
  • [ 1798-85-2 ]
YieldReaction ConditionsOperation in experiment
81% 1.0 M Diethyl zinc in hexanes (27.3 ml, 27.3 mmol) was added to a solution of 2,4, 6- [TRICHLOROPHENOL] (5.4g, 27.3 mmol) in dichloromethane (100 ml) at-40C. After stirring for 15 minutes, diiodo-methane (2.2 mL, 27.3 mmol) was added at-40C and stirred for an additional 15 minutes. 1-Bromo-3-vinyl-benzene (2.5 g, 13.7 mmol) was then added to the reaction mixture, allowed to warm to room temperature, and left stirring overnight. The reaction mixture was diluted with dichloromethane, washed with 1N [HC1] (2X), saturated sodium bicarbonate (2X), saturated sodium sulfite, 1N sodium hydroxide, and saturated brine, dried over magnesium sulfate, filtered and concentrated. GC-MS revealed that the reaction mixture contained [L-BROMO-3-CYCLOPROPYL-BENZENE] and 1-bromo-3-vinyl-benzene. To remove the bromo-3-vinyl-benzene, the crude mixture was reacted with potassium permanganate. A solution of potassium permanganate/water (1.5 g/20 mL) was added drop-wise to a solution of the crude mixture [(-3.] 5 g) in THF (40 mL) at [0C] and then allowed to warm to room temperature. After 1 hour, the reaction was diluted with diethyl ether, washed with water and saturated brine, dried over anhydrous sodium sulfate filtered and concentrated. Purication by flash column chromatography eluted with 100 hexanes afforded [1-BROMO-3-CYCLOPROPYL-BENZENE] (2.20g, [81%).] 1.6 M n-Butyllithium in hexanes (3.2 mL, 5.1 mmol) was added drop-wise to a solution of [L-BROMO-3-CYCLOPROPYL-BENZENE] [AT-78C] and stirred for 1 hour. This reaction mixture was then transferred via canula to a 250 mL round bottom flask equipped with a stirrer bar approximately [1/4 FULL] of solid carbon dioxide and stirred and for 1 hour. The reaction mixture was concentrated and then the residue was diluted with water. The aqueous layer was washed with dichloromethane [(3X),] acidified with 1 N [HC1] to [PH-2,] and extracted with ethyl acetate. The organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford 3-cyclopropyl-benzoic (356 mg, 43%, white [SOLID). IH NMR (DMSO), 6] (ppm): 12.90 (bs, 1H), 7.71 (d, 1H), 7.64 (s, 1H), 7.34 (m, 2H), 2.01 (m, 1H), 0.99 (m, 2H), 0.70 (m, 2H).
With iodine; copper; In toluene; for 140h;Heating / reflux; Iodine (0.335 g, 1.32 mmol), diiodomethane (4.3 mL, 53.0 mmol) and 3- bromostyrene (5g, 26.4 mmol) were added successively to a suspension of copper (7.5 g, 118.8 mmol) in toluene (50 mL). The mixture was refluxed for 140h, then filtered and concentrated in vacuo. The residue was distilled under reduced pressure to afford 3-bromo-1-cyclopropylbenzene (0.55g, 10%) as a colorless oil. ¹H NMR (CDC13) 8 : 7.35-7.25 (m, 1 H); 7.25-7.20 (m, 1 H); 7.15-7.05 (m, 1H) ; 7.05- 6.95 (m, 1 H); 1.95-1.85 (m, 1H) ; 1.05-0.95 (m, 2H) ; 0.75-0.65 (m, 2H).
  • 16
  • [ 1798-85-2 ]
  • [ 841-95-2 ]
  • C24H27NO3 [ No CAS ]
  • 17
  • [ 871793-69-0 ]
  • [ 1798-85-2 ]
  • 4-(3-cyclopropyl-phenyl)-6-propyl-pyrimidine-2-carbonitrile [ No CAS ]
  • 18
  • [ 945717-13-5 ]
  • [ 1798-85-2 ]
  • [ 945717-15-7 ]
YieldReaction ConditionsOperation in experiment
58% To a solution of <strong>[1798-85-2]m-bromophenylcyclopropane</strong> (synthesised as described in J. Org. Chem. 1976, 41, 2262-2266) (100 mg, 0.51 mmol) in dry THF (3 ml) at -78 C. was added nBuLi (317 mul, 1.6M solution in hexane, 0.51 mmol) dropwise. The reaction mixture was stirred at -78 C. for 10 min and then a solution of 3-(4-tert-butylbenzyl)-[1,2,3]oxathiazolidine 2,2-dioxide (109 mg, 0.41 mmol) in THF (1 ml) was added dropwise. The reaction mixture was warmed to 0 C. over 3 hours and then quenched with 5 ml 20% (v/v) H2SO4. The reaction mixture was warmed to 60 C. overnight and then cooled to RT and poured into water. The aqueous phase was made basic with 1N NaOH and then extracted with ethyl acetate. The organic layers were combined, washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give a crude residue which was purified by flash column chromatography to give (4-tert-butylbenzyl)-[2-(3-cyclopropylphenyl)-ethyl]-amine (72 mg, 58%) as a colorless oil. MS (ISP) 308.4 (M+H)+.
  • 19
  • [ 1798-85-2 ]
  • [ 1309474-99-4 ]
  • [ 1309475-03-3 ]
YieldReaction ConditionsOperation in experiment
Example 1-2: 4-((5R,7S)-7-{3-cyclopropylphenyl)-7-hydroxy-6,7-dihydro-5H- pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrileTo a solution of <strong>[1798-85-2]1-bromo-3-cyclopropyl-benzene</strong> (0.018 ml, 0.124 mmol) in THF (0.2 ml) cooled to -78 C was added a solution of 1.6 M t-BuLi (0.155 ml, 0.249 mmol). The crude was stirred at -78 C for 2 hrs. To this solution was add a solution of 3-fluoro-4-((R)-7-oxo- 6,7-dihydro-5H pyrrolo[1 ,2-c]imidazol-5-yl)-benzonitrile (20 mg, 0.083 mmol) in THF (0.2 ml). The crude was stirred at -78 C for 1 hr, then at 0 C for 1 hr and room temperature for 1 hr. This reaction was quenched with water and extract the aq. with CH2CI2. The organic layer was dried over Na2S04, filtered, and concentrated. The crude was purified via preparation plate using 10% (2M NH3 in MeOH) / CH2CI2. The entitled product (4 mg) was isolated as the major diastereomer. MS 360.1 (M+H); LCMS condition B, retention time 1.16 min. 1 H NMR (400 MHz, CDCI3) delta ppm 0.52 - 0.65 (m, 2 H), 0.85 - 0.95 (m, 2 H), 1.74 - 1.91 (m, 1 H), 2.57 (br. s., 1 H), 2.92 (d, 1 H), 3.30 (dd, 1 H), 5.73 (d, 1 H), 6.91 (s, 1 H), 6.96 (ddd, 1 H), 7.12 (t, 1 H), 7.16 - 7.28 (m, 3 H), 7.29 - 7.41 (m, 2 H), 7.42 - 7.53 (m, 1 H).
  • 20
  • [ 2039-86-3 ]
  • [ 1372474-95-7 ]
  • [ 1798-85-2 ]
  • 21
  • [ 1798-85-2 ]
  • [ 1584150-10-6 ]
  • [ 1584150-21-9 ]
YieldReaction ConditionsOperation in experiment
48% With tris-(dibenzylideneacetone)dipalladium(0); potassium carbonate; XPhos; In tert-butyl alcohol; at 80℃;Inert atmosphere; A stirred suspension oflntermediate B-4 (201.8 mg, 0.647 mmol), <strong>[1798-85-2]1-bromo-3-cyclopropylbenzene</strong> (246.7 mg, 1.252 mmol), Pd2(dba)3 (58.5 mg, 0.064 mmol), 2-(dicyclohexylphosphino)-2',4',6'-triisopropylbiphenyl ("X-Phos") (30.7 mg, 0.064 mmol)and potassium carbonate (414.7 mg, 3.00 mmol) in t-BuOH (4.0 mL) was degassed(pump/N2 x 3) and then heated to 80 oc overnight. The reaction mixture was cooled to20 room temperature. The mixture was diluted with EtOAc, filtered through a 4 )lmmembrane filter, concentrated, and then dried under vacuum. The residue was purifiedby flash chromatography (Teledyne ISCO CombiFlash Rf, gradient ofO% to 100% using solvent A/B=heptane/EtOAc over 15 column volumes, REDISEP Si02 40g, loaded asDCM solution). Obtained Intermediate B-12A (134.0 mg, 48%) as a tan solid: HPLC:RT=2.218 min (Waters SunFire C18 2.1x30mm, MeOH/H20/0.1% TFA, 2min gradient,wavelength= 254 nm); MS(ES): m/z= 372/374 [M-t-Bu+ It; 1H NMR (400 MHz,5 chloroform-d) 8 7.05-7.15 (m, IH), 6.59 (d, J=7.70 Hz, IH), 6.47-6.55 (m, 2H), 5.61 (d,J=7.26 Hz, IH), 4.53-4.65 (m, IH), 4.26-4.33 (m, IH), 3.66 (dd, J=9.57, 11.77 Hz, IH),1.75-1.85 (m, IH), 1.46 (s, 9H), 0.85-0.97 (m, 2H), 0.57-0.71 (m, 2H).
  • 22
  • [ 1798-85-2 ]
  • [ 62673-31-8 ]
  • [ 1621097-08-2 ]
YieldReaction ConditionsOperation in experiment
>99%Spectr. With C30H21F6N2NiO2P; In tetrahydrofuran; at 70℃; for 24h;Schlenk technique; Inert atmosphere; General procedure: A Schlenk flask was charged with an appropriate amount of complex 2b (0.016mmol, 2.0mol%) and the corresponding bromo or iodo arene (0.77mmol). The flask was cycled with nitrogen and vacuum. Afterwards a THF solution of benzylzinc bromide (2.2mL, 1.1mmol, 0.5M in THF) was added. The flask was sealed and heated at 70C for 24h. After that time, the mixture was cooled, and dichloromethane and water were added. The aqueous layer was extracted with dichloromethane and the collected organic layers were washed with water and dried with Na2SO4. The coupling product was confirmed by GC-MS (with n-dodecane as internal standard) and NMR analysis. The analytical properties of the products are in agreement with literature data [6a,24].
  • 23
  • [ 1798-85-2 ]
  • rac-1-((2S,3R,4R)-4-amino-2-cyclopropyl-3-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone hydrobromide [ No CAS ]
  • rac-1-((2S,3R,4R)-2-cyclopropyl-4-((3-cyclopropylphenyl)amino)-3-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
53.3% With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; DavePhos; In 1,4-dioxane; at 100℃; for 1.66667h;Inert atmosphere; A mixture of rac- I -((2S,3R,4R)-4-am ino-2-cyclopropyl-3-methyl-3,4-dihydroqu inolin- I (2H)- yl)ethanone, hydrobromide (for a preparation see Intermediate 125, 50.3 mg, 0.155 mmol), 1-bromo- 3-cyclopropylbenzene (0.041 mL, 0.309 mmol), DavePhos (6.9 mg, 0.018 mmol), Pd2(dba)3 (23.3mg, 0.025 mmol) and sodium tert-butoxide (38.1 mg, 0.396 mmol) in I ,4-dioxane (1 mL) was heated under nitrogen at 100 C for 100 mm. The mixture was allowed to cool to rt and was filtered through a 2.5 g celite cartridge, washing with ethyl acetate (3x5 mL). The combined filtrate was evaporated under a stream of nitrogen and the residue was re-dissolved in methanol/DMSO (1 mL, 9:1) and was purified by MDAP (Formic). The required fraction was evaporated under a stream of nitrogen to givethe desired product as an orange/brown gum (29.7 mg, 0.082 mmol, 53.3%). LCMS (2 mm Formic): Rt = 1 .29 mi [MH] = 361.
  • 24
  • [ 1798-85-2 ]
  • 2-[(2-aminoethyl)amino]-N-[5-(3-cyclopropylphenyl)pyridin-2-yl]pyridine-5-carboxamide [ No CAS ]
  • 25
  • [ 1798-85-2 ]
  • C27H31N5O3 [ No CAS ]
  • 26
  • [ 851524-96-4 ]
  • [ 1798-85-2 ]
  • 5-(3-cyclopropylphenyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water; at 90℃; for 16h;Inert atmosphere; Monomer Synthesis Procedure A 1-Bromo-3-cyclopropylbenzene (0.20 g, 1.4 mmol, 1.0 eq.), 6- Aminopyridine-3-boronic acid (0.28 g, 1 .4 mmol, 1 .0 eq.) and C52C03 (1 .41g, 4.3 mmol, 1 .5 eq.) were added to a mixture of dioxane (8 mL) and water (2 mL) which was subsequently degassed with argon for 30 mi Pd(PPh3)4 (0.087 g, 4.3 mmol, 0.05 eq.) was added and the reaction mixture was heated to 90 C for 16 h. After completion of the reaction, the reaction mixture was filtered and the filtrate was concentrated under reducedpressure. The resulting crude material was dissolved in ethyl acetate (100 mL) and washed with cold water (100 mL) and brine (25 mL). The organic layer was dried over Na2504 and concentrated under reduced pressure to obtain crude product. This material was purified by flash chromatography (over silica gel 100-200 mesh) eluting with 25 % ethyl acetate in petroleumether to obtain pure 5-(3-cyclopropylphenyl)pyridin-2-amine (80 mg; 37%).
  • 27
  • [ 944401-75-6 ]
  • [ 1798-85-2 ]
  • 5-(3-cyclopropylphenyl)-3-fluoropyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
21.5% With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 80℃; for 2h;Inert atmosphere; Monomer Synthesis V Pd(PPh3)4 (1.1 g, 1.03 mmol, 0.1 eq.) and Na2CO3 (1.6 g, 15.37mmol, 1.5 eq.) were added to a stirred solution of 1-bromo-3- cyclopropylbenzene (2.0 g, 10.25 mmol, 1 .0 eq.) and 3-fluoro-5-(4,4,5,5- tetramethyl-1 ,3,2-dioxaborolan-2-yl)pyridin-2-amine (2.6 g, 11.28 mmol, 1.1eq.) in a mixture of dioxane (3 mL) and water (1 .5 mL) previously degassed with argon for 30 mm. The reaction mixture was heated to 80 C for 2 h after which time it was allowed to cool to RT. The reaction mixture was then filtered through a bed of celite and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (100 mL) thenwashed with water and brine (100 mL each). The organic layer was dried over Na2504 and concentrated under reduced pressure to afford crude product. This material was purified by flash chromatography (over silica gel 100-200 mesh) eluting with 100 % EtOAc to afford pure 5-(3- cyclopropylphenyl)-3-fluoropyridin-2-amine (500 mg; 21 .5 %)
  • 28
  • [ 1798-85-2 ]
  • [ 97985-66-5 ]
  • 5-(3-bromophenyl)-4,5-dihydro-1,2-oxazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
20.3%Spectr.; 42.2%Spectr. With trifluoroacetic acid; sodium nitrite; In chloroform; at 0 - 20℃; General procedure: Sodium nitrite, 0.69 g (0.01 mol), was added in portions over a period of 10-15 min to a mixture of 0.01 mol of arylcyclopropane 1a-1l, 5.2 g of trifluoroacetic acid, and 15 mL of chloroform, cooled to 0-5 C.The mixture was allowed to warm up to 20 C, kept for1 h at that temperature, and poured into 100 mL of cold water. The organic phase was separated, the aqueousphase was extracted with chloroform (2 × 10 mL), the extracts were combined with the organic phase,washed with water (2 × 30 mL), and dried over MgSO4, the solvent was removed, and the residue was analyzed by 1H NMR. Compound 2l was isolated by crystallization. The compositions of the reaction mixtures are given in Table 1. The physical constants and spectral characteristics of 2a [16], 2b [30], and 2l [28] coincided with published data. 5-(3-Bromophenyl)-4,5-dihydro-1,2-oxazole (2c). Viscous oily material. 1H NMR spectrum, delta, ppm:2.98 d.d.d (1H, 4-H, J = 2.0, 7.4, 17.8 Hz) and 3.46 d.d.d (1H, 4-H, J = 2.0, 10.5, 17.8 Hz), 5.51 d.d (1H, 5-H, J = 7.4, 10.5 Hz), 7.23 s (1H, 3-H), 7.23-7.28 m (3H, Harom), 7.49 m (1H, Harom). Found, %:C 47.33, 47.51; H 3.36, 3.42; N 5.91, 6.02. C9H8BrNO. Calculated, %: C 47.82; H 3.57; N 6.20.
  • 30
  • bismuth(III) chloride [ No CAS ]
  • [ 1798-85-2 ]
  • [ 1632197-03-5 ]
  • 31
  • [ 1798-85-2 ]
  • [ 171364-81-1 ]
  • 1-(3-cyclopropylphenyl)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
A bottom flask was charged with magnesium (148 mg, 6.09 mmoi) and anhydrous THF (0.5 mL),to the stirred mixture was added isopropylmagnesium chloride solution (catalytic amount), then asolution of i-hromo-3-cyclopropyibenzee (1 g, 5.07 mmoi) in THF (4.5 mL) was added slowlywith an injection syringe under nitrogen to keep the temperature containing 50CC 60 C. Theresulted mixture was stirred at 70C fbr another 30 mins and then was allowed to cool to 20CC.The resulting Grignard reagent was added to a solution of I -(4-4,4,5 ,5-tetramethyl- 1,3,2-dioxaboroian-2--yi)phenyi)ethanone (600 mg, 2.54 mmoi) in THIF (5 mL) drop-wise at 0CC, themixture was stirred at 0C to 25 ?C for 2 hours before quenched by ice-water (10 mL) slowly.The mixture was extracted with ethyl acetate (20 mL x 3), and the combined organic layers werewashed with brine (20 mL), dried over sodium sulfate, filtered and concentrated to afford thecrude product, which was purified on silica gel column chromatography (ethyl acetate / pet. ether0% 20%) to give I -(3-cyclopropylphenyi)- 1 -(4-(4,4,5,5-tetramethyi-i ,3,2-dioxahoroian-2-yi)phenyi)ethanol. ?H NMR (400MHz, CDC13) d = 7,77 (d, J=8.3 Hz, 2H), 7.43 (d, J=8.3 Hz,2H), 7.22 - 7.06 (m, 3H), 6S3 .. 6.86 (m, 1H), 1.94 (s, 3H), 1.90 - 1.81 (m, 1H), 1.34 (s, 12H),0.97 - 0.90 (rn, 2H), 0,73 - 0.61 (m, 2H) ppm.
  • 32
  • [ 5419-55-6 ]
  • [ 1798-85-2 ]
  • [ 1049730-10-0 ]
YieldReaction ConditionsOperation in experiment
60% A solution of <strong>[1798-85-2]1-bromo-3-cyclopropylbenzene</strong> (2.0 g, 10 mmol) in THF (24 mL) was cooled to -78 C, n-butyllithium solution in hexanes (1.6 M, 12.7 mL, 20.3 mmol) was added and the mixture was stirred for 30 min before adding triisopropylborate (3.06 mL, 13.2 mmol). The mixture was stirred for 45 min and then the reaction mixture was warmed to room temperature. After 1 h the reaction was quenched with aqueous 2 M HCl (100 mL) and extracted with EtOAc (3 * 100 mL). The combined organic layers were passed through a hydrophobic frit and concentrated in vacuo. The residue was recrystallised from the minimum amount of hot TBME and the crystals were dried in vacuo to afford 6d (1.16 g, 60%): LCMS (System A) RT = 0.80 min, 97% (no mass ion observed); 1H NMR (CD3OD, 400 MHz) 7.52-7.44 (1H, m), 7.37-7.28 (1H, m), 7.25-7.15 (1H, m), 7.12-7.06 (1H, m), 1.94-1.84 (1H, m), 0.97-0.88 (2H, m), 0.69-0.63 (2H, m).
  • 33
  • [ 1798-85-2 ]
  • 4-(3-cyclopropylphenyl)dihydrofuran-2(3H)-one [ No CAS ]
  • 34
  • [ 1798-85-2 ]
  • (R)-4-(3-cyclopropylphenyl)dihydrofuran-2(3H)-one [ No CAS ]
  • 35
  • [ 1798-85-2 ]
  • methyl 2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-6-carboxylate [ No CAS ]
  • methyl 1-(3-cyclopropylphenyl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-6-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
133 mg With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); XPhos; In toluene; at 100℃; for 16h;Inert atmosphere; A mixture of methyl 2, 3-dihydro-lH-pyrido [2, 3- b] [1, 4] oxazine-6-carboxylate (193 mg, 0.99 mmol), l-bromo-3- cyclopropylbenzene (380 mg, 1.93 mmol), Pd2(dba)3 (45 mg, 0.05 mmol), XPHOS (52 mg, 0.11 mmol), K3PO4 (423 mg, 1.99 mmol) and toluene (10 mL) was stirred under nitrogen atmosphere at 100C for 16 h. After being cooled^ the mixture was poured into water and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The residue was purified by column chromatography (silica gel, eluted with 30% - 70% EtOAc in hexane) to give the title compound (133 mg, 0.429 mmol, 43.1%) as pale yellow solids. (3703) MS (ESI+), found 311.3 (M+H) (3704) 1H NMR (300 MHz, CDC13) 5:0.66-0.75 (2H, m) , 0.98-1.09 (2H, m) , 1.83-1.97 (1H, m) , 3.74-3.80 (2H, m) , 3.92 (3H, s) , 4.49-4.55 (2H, m) , 6.92-6.98 (2H, m) , 6.99-7.07 (2H, m) , 7.29-7.38 (1H, m) , 7.60 (1H, d, J = 7.9 Hz) .
 

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