214045-86-0|1-Chloro-6-fluoroisoquinoline| Ambeed

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Quality Control of [ 214045-86-0 ] Purity: 97% SDS Specification

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Product Details of [ 214045-86-0 ]

CAS No. :	214045-86-0
Formula :	C₉H₅ClFN
M.W :	181.59
SMILES Code :	FC1=CC2=C(C(Cl)=NC=C2)C=C1
MDL No. :	MFCD09959717
InChI Key :	QZBWBBHQRLUOTM-UHFFFAOYSA-N
Pubchem ID :	21901072

Safety of [ 214045-86-0 ]

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

Computational Chemistry of [ 214045-86-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	10
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	46.71
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	12.89 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.08
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.16
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	3.45
Log P_o/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.	2.83
Log P_o/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	3.5
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.0

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.57
Solubility	0.0485 mg/ml ; 0.000267 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.	-3.1
Solubility	0.144 mg/ml ; 0.000792 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	-4.59
Solubility	0.00461 mg/ml ; 0.0000254 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.	-5.16 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	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<1.0
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)	1.6

Application In Synthesis of [ 214045-86-0 ]

* 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 [ 214045-86-0 ]

[ 214045-86-0 ] Synthesis Path-Downstream 1~19

1
[ 214045-86-0 ]
[ 56008-20-9 ]
1-(3-chloro-isoquinolin-6-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
9%	With sodium hydride; In N,N-dimethyl-formamide; at 160℃; for 0.333333h;Microwave irradiation;	Example 14 1-(3-chloro-isoquinolin-6-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one; To a solution of <strong>[214045-86-0]1-chloro-6-fluoro-isoquinoline</strong> (0.0847 g, 0.47 mmol) in DMF (2 mL) are added pyrrole (0.1 g, 0.56 mmol) and NaH (0.028 g, 0.71 mmol). The reaction mixture is microwaved at 160 C. for 20 min. The reaction mixture is cooled to RT, and treated with NH4Cl (satd. aq., 2 mL). The aqueous phase is extracted with EtOAc (2×). The combined organic layers are washed with brine, and dried over MgSO4. The solvent is evaporated and the residue is dried under vacuum. Purification of the crude material using a Biotage column (0-50% EtOAc/hexanes) affords 0.014 g (9%) of 1-(3-chloro-isoquinolin-6-yl)-3,6,6-trimethyl-1,5,6,7-tetrahydro-indol-4-one. LC/MS m/z=339 [M+H]+, RT=4.01 min.

References: [1]Patent: US2008/70935,2008,A1 .Location in patent: Page/Page column 49.

2
[ 18638-99-8 ]
[ 214045-86-0 ]
1-(3,4,5-trimethoxybenzyl)amino-6-fluoro-isoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With sodium t-butanolate;2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; bis(dibenzylideneacetone)-palladium(0); In toluene; at 120℃; for 0.666667h;Microwave irradiation;	Example 15 1-amino-6-fluoro-isoquinoline; A suspension of <strong>[214045-86-0]1-chloro-6-fluoro-isoquinoline</strong> (0.9708 g, 5.35 mmol), 3,4,5-methoxybenzylamine (0.92 mL, 5.35 mmol), Pd(dba)2 (0.31 g, 0.54 mmol), BINAP (0.34 g, 0.54 mmol) and NaOtBu (1.54 g, 16.05 mmol) in toluene (15 mL) is microwaved at 120 C. for 40 min. The reaction mixture is cooled to RT, then filtered through a pad of Celite. The filter cake is rinsed with EtOAc. The filtrate is concentrated and the crude product is purified by chromatography using a Biotage column (10-60% EtOAc/hexanes) to afford 1.26 g (69%) of 1-(3,4,5-trimethoxybenzyl)amino-6-fluoro-isoquinoline. m/z=343 [M+H]+.

References: [1]Patent: US2008/70935,2008,A1 .Location in patent: Page/Page column 49.

3
[ 214045-86-0 ]
[ 683-60-3 ]
[ 630422-61-6 ]

Yield	Reaction Conditions	Operation in experiment
54%	In DMF (N,N-dimethyl-formamide);	Some 6-alkoxy-l-chloro isoquinolines were prepared by a direct, ipso displacement of the6-fluoro-1-chloroisoquinoline with the corresponding alkoxide metal ions such as potassium tert-butoxide (53%) and sodium isopropoxide (54%). The6-fluoro-1-chloroisoquinoline was subjected to an aromatic nucleophilic displacement with sodium isopropoxide and potassium tert-butoxide in DMF to give the corresponding 6-isopropoxyl (54%) : 1H NMR (400 MHz, CHLOROFORM-d)8 ppm 1.43 (d, J=6. 11 Hz, 6 H) 4.76 (m,J=6. 11 Hz,1 H) 7.08 (d, J=2. 45 Hz,1 H) 7.29 (dd, J=9. 29, 2.45 Hz, 1 H) 7.50 (d, J=5. 62 Hz, 1 H) 8.18 (d, J=5. 87 Hz,1 H) 8.24 (d, J=9. 29 Hz,1 H)

References: [1]Patent: WO2003/99274,2003,A1 .Location in patent: Page 275-276.

4
[ 1008-86-2 ]
[ 214045-86-0 ]

Yield	Reaction Conditions	Operation in experiment
43%	With trichlorophosphate; In benzene;	In general, the 6-fluoro and 6-alkyl isoquinolines used in the following experiments were prepared via a Pomeranz-Fritsch synthesis (Typical procedure: Preparation of optically active 8,8-disubstituted 1, 1-biisoquinoline, K.Hirao, R. Tsuchiya, Y. Yano, H. Tsue, Heterocycles 42(1) 1996,415-422) as outlined below. The products were converted into the 1-chloro derivatives via N-oxide intermediates as described elsewhere. General Synthetic Scheme EMI271.1Reagents and reaction conditions: (a) reflux in benzene, azeotropic removal of water; (b) first step: ethyl chloroformate, trimethyl phosphite in THF, second step: titanium tetrachloride in chloroform; (c) MCPBA inCH2CI2 ; (d) POCl3 in benzene
35%		To a solution of 6-fluoroisoquinoline N-oxide (3 g, 18 mmol) in CHCl3 (50 mL) is added phosphorus oxychloride (5 mL, 54 mmol). The reaction mixture is refluxed for 2 h. The reaction mixture is poured into ice, and the pH is brought to pH 8-9 with 5 M NaOH. The aqueous phase is extracted with CH2Cl2 (3×). The combined organic layers are dried over MgSO4, and evaporated. Purification of the crude product by Biotage column eluted with 0-30% EtOAc/hexanes afforded 1.06 g (35%) of 1-chloro-6-fluoro-isoquinoline. LC/MS m/z=182 [M+H]+.

References: [1]Patent: WO2003/99274,2003,A1 .Location in patent: Page 271-272.
[2]Patent: US2008/70935,2008,A1 .Location in patent: Page/Page column 48-49.

5
[ 214045-86-0 ]
[ 769-92-6 ]
[ 848841-45-2 ]

Yield	Reaction Conditions	Operation in experiment
56%	In 1,4-dioxane; water; butan-1-ol; at 80℃;	1 B) (4-TERT-BUTVL-PHENVL)-(6-FLUORO-ISOQUINOLIN-1-VL)-AMINE 1-CHLORO-6-FLUORO-ISOQUINOLINE (1 g, 6.13 MMOL) is dissolved in n-BuOH (20 mL) and 4-T-BUTYL-ANILINE (1. 1 g, 6.74 MMOL). 4 N HCI (1 mL) in dioxane (1 mL) is added dropwise. The resulting mixture is heated at 80C overnight. The mixture is rotary evaporated, and the residues dissolved in ethyl acetate, washed with saturated NAHC03, brine and dried over MGS04. The solute is removed and after CONCENTRATION IN VACUO, the organic layer is further purified by silica gel column (hexane 90% to 10% ethyl acetate/hexane) to afford a yellow solid (900 mg, 56%). M+H+ = 295.3. 'H NMR (300 MHz) (DMSO); 8 1.29 (s, 9H), 7.13 (d, 1H, J=6 Hz), 7.34 (d, 2H, J=8.67 Hz), 7.50 (m, 1H), 7.60 (dd, 1H, J=2.64, 9. 8 HZ) =7. 72 (d, 2H, 8.67 HZ), 7. 96 (d, 1H, 5.65 Hz), 8. 61 (dd, 1H, J=5.46, 9.23 Hz), 9.16 (s, 1H).; 21 B) (4-TERT-BUTVL-PHENVL)-(6-FLUORO-ISOQUINOLIN-1-VL)-AMINE A solution of <strong>[214045-86-0]1-chloro-6-fluoro-isoquinoline</strong> (1 g, 6.13 MMOL) and 4-tert-butyl- aniline (1. 1 g, 6.74 MMOL) in nBuOH (20 mL) and 4N HCI/DIOXANE (1 mL) is heated at 80C overnight. The mixture is concentrated and the residue is made basic with sat. NaHC03 and extracted with EtOAc. The organic layer is dried, concentrated and purified by silica gel column (Hexane to 10% ETOAC/HEXANE) to afford yellow solid (900 mg, 56%). M+H+=295. 3. H NMR (400 MHz, DMSO-D6) 5 1.29 (s, 9H), 7.13 (d, 1H, J= 6 Hz), 7.34 (d, 2H, J= 8.67 Hz), 7.50 (m, 1 H), 7.60 (dd, 1 H, J = 2.64, 9.8 Hz) 7.72 (d, 2H, J = 8.67 Hz), 7.96 (d, 1 H, J= 5.65 Hz), 8.61 (dd, 1H J=5.46, 9.23Hz), 9.16 (s, 1H).

References: [1]Patent: WO2005/28444,2005,A1 .Location in patent: Page/Page column 48; 70.

6
[ 214045-85-9 ]
[ 214045-86-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	With hydrogenchloride; trichlorophosphate; In 1,4-dioxane; water; acetonitrile; at 50℃;	1 A) 1-CHLORO-6-FLUORO-ISOQUINOLINE 6-FLUORO-2H-ISOQUINOLIN-1-ONE (1.3 g, 7.97 MMOL) (for preparation, see PCT/GB02/00514 and WO 02/062816) is suspended in CH3CN (20mL) and then POCI3 (3.7 g, 23.9 MMOL). 4 N HO (2 mL) in dioxane (2 mL) is added dropwise. The resulting mixture is heated at 50C overnight with stirring. The reaction mixture is poured into a saturated NAHC03 SOLUTION and is extracted with ethyl acetate. The organic layer is concentrated to afford an orange solid (1.1 g, 78%). M+H+ = 181.8. 'H NMR (300 MHz) (CDC13) ; 8 7.42 (m, 2H), 8.26 (m, 3H).; 21A) 1-CHLORO-6-FLUORO-ISOQUINOLINE A solution of 6-FLUORO-2H-ISOQUINOLIN-1-ONE (PCT/GB02/00514 ; WO 02/062816) (1.3 g, 7.97 MMOL) and POC13 (3.7 g, 23.9 MMOL) in CH3CN (20 mL) and 4N HCI/dioxane (2 mL) is heated at 50C overnight. The reaction mixture is diluted with a NaHC03 solution and extracted with EtOAc. The organic layer is concentrated to afford an orange solid (1.1 g, 78%). M+H+=181. 8. H NMR (400 MHz, CDCL3)No. 7.42 (m, 2H), 8.26 (m, 3H).

References: [1]Patent: WO2005/28444,2005,A1 .Location in patent: Page/Page column 47-48; 69-70.

7
[ 98-03-3 ]
[ 214045-86-0 ]
[ 1354830-99-1 ]

Yield	Reaction Conditions	Operation in experiment
		Following the same LDA deprotonation protocol (preparation of Example 203) of 1- chloro-6-fluoro isoquinoline described previously, the initial anion was quenched with 2-thiophenecarboxaldehyde instead, to give 1-chloro-6-fluoro isoquinolin-5-yl-thiophen-2-yl-methanol. The material was oxidized to the 1-chloro-6-fluoro- isoquinolin-5-yl-thiophen-2-yl-methanone usingMn02 in benzene in 49.6% overall yield after chromatographic purification. LC/MS rt-min(MH) [method C]: 2.98(292).'H NMR (400 MHz, CHLOROFORM-D)8 ppm 7.12 (dd, J=4. 89,3. 91 Hz,1 H) 7.40 (m,1 H) 7.53 (m, 1 H) 7.56 (dd, J=5. 87,0. 73 Hz,1 H) 7.82 (dd, J=5.01, 1.10 Hz,1 H) 8.27 (d, J=5. 87 Hz,1 H) 8.54 (ddd, J=9. 29,5. 38,0. 73 Hz,1 H). Ipso nucleophilic aromatic displacement of the fluorine atom was accomplished in a solution of excess of potassium methoxide to give, mainly 1-chloro-6-methoxy- isoquinolin-5-yl-thiophen-2-yl-methanone along with 25-33% of 1,6-dimethoxy- isoquinolin-5-yl-thiophen-2-yl-methanone. The crude material (77mg) was used in the alkylation step with the tripeptide without further purification.

References: [1]Patent: WO2003/99274,2003,A1 .Location in patent: Page 290-291.

8
[ 214045-86-0 ]
[ 624-92-0 ]
[ 1354831-01-8 ]

Yield	Reaction Conditions	Operation in experiment
		To the solution of 100 mg 1-Chloro-6-fluoro-isoquinoline (0.55 mmole) in 2 ml dry THF at-78 C was added LDA in THF (1.3 eq). Dark brown solution was formed, then disulfide was added and the color of solution changed to greenish, then light brown. The reaction was quenched with 2 mL of water and 2mL ofNH4Cl, extracted with ethyl acetate, dried over sodium sulfate. The solvent was evaporated under vacuum and the resulted residue was used as crude. LC/MS rt-min(MH+) : 2.23 (228) [method B]. The crude material was redissolved in 2 ml of dry THF at-78 C and 1.3 eq. of KOMe was added then the reaction mixture was allowed to warmed up to RT, stirred overnight. The reaction mixture was diluted with ethyl acetate and washed with brine, dried over sodium sulfate. 104 mg was obtained (79%). LC/MS rt-min (MH+) : 2.04 (240) [method B]. The intermediate, 1-chloro-5-methylthio-6-methoxy isoquinoline was subjected to the tripeptide alkylation protocol described previously. Following the general procedure, 70.0 mg of yellow solid was obtained (42.7%). LC/MS rt-min(MH+) : 2.65 (760) [methodB].'H NMR (400 MHz, CHLOROFORM-D)8 ppm 0.94 (m,11 H) 1.17 (s, 9 H) 1.26 (m, 2 H) 1.39 (m,1 H) 1.83 (dd, J=8. 07,5. 62 Hz,1 H) 2.01 (m, 2 H) 2.23 (s, 3 H) 2.45 (m,1 H) 2.79 (m,1 H) 3.94 (s, 3 H) 3.97 (d, J=3. 91 Hz,1 H) 4.15 (s,1 H) 4.25 (d,J=11.74 Hz,1 H) 4.36 (dd, J=9. 66,7. 21 Hz,1 H) 4.99 (d,J=10. 27 Hz, 1 H) 5.12 (d,J=16. 87 Hz,1 H) 5.69 (m,1 H) 5.74 (s,1 H) 7.08 (d, J=9. 05 Hz,1 H) 7.83 (m, 2 H) 8.06 (d, J=9. 05 Hz, 1 H).

References: [1]Patent: WO2003/99274,2003,A1 .Location in patent: Page 289-290.

9
[ 214045-86-0 ]
[ 629-19-6 ]
[ 630419-50-0 ]

Yield	Reaction Conditions	Operation in experiment
36%		To a chilled(-78 C) solution of 1-chloro-6-fluoro isoquinoline (59mg, 0.32 mmol) in 2 mL of THF was added LDA solution in cyclohexane (1.5 Molar, 0.23 mL, 0.35 mmol). The orange solution was stirred for 2 hrs before it was treated with n-propyl disulfide (60ZL, neat material, excess). The reaction was allowed to warm to room temperature over 30 min. It was quenched with a solution of half saturatedNH4CI, the organic residues were extracted into ethyl acetate. LC-MS analysis indicated about50% conversion into the desired product along with mainly starting material. The desired product was purified by a short column (4 cm X 2 cm, silica gel type-H) eluted with 5% ether in hexanes, 29mg (36% yield) of the desired product was obtained. LC/MSRt-min(MH+) [method C] : 3.79(256).'H NMR (400 MHz, CHLOROFORM-D)8 ppm 0.96 (t, J=7. 34 Hz, 3 H) 1.52 (m, 2 H) 2.86 (m, 2 H) 7.45 (dd, J=9.29, 8.56 Hz,1 H) 8.34 (d,J=0. 73 Hz, 2 H) 8.37 (m,1 H).
		The following procedure is equally applicable to other 5-alkylthio-6-alkoxy isoquinolines by changing the reagents shown here. To a solution of 1-chloro-6- fluoro isoquinoline (88mg, 0.48 mmol) in 2.0mL THF under nitrogen at-78 C was added LDA (1.5 Molar in cyclohexane, 0.42 mL, 0.63 mmol) forming a dark brownish solution. Neat n-propyl disulfide(85, uL, excess) was introduced after it was stirred at-78 C for 30 min. The reaction was allowed to warm to room temperature over a period of 30 min. It was quenched with a solution of half saturatedNH4Cl, the organic residues were extracted into ethyl acetate. The organic layers were combined and dried under vacuum to 50 microns (Hg). The crude product was taken into 2 mL of THF, cooledto-78 C, added with excess potassium ethoxide (60mg). The isoquinoline intermediate was finally purified by a silica gel column (type-H, Merck) eluted with ether-hexanes mixture, 32.2mg (24%) of the pure compound was obtained. LC-MS showed 1-chloro-5-propylthio-6-ethoxyl isoquinoline at rt-min(MH+) [method C]: 3.77 (282).'H NMR (400 MHz, CHLOROFORM-D)8 ppm 0.94 (t, J=7. 34 Hz, 3 H)1. 46 (m, 2 H) 1.55 (t, J=6. 97 Hz, 3 H) 2.83 (t, J=7. 21 Hz, 2 H) 4.32 (q,J=6. 85 Hz, 2 H) 7.36 (d,J=9. 29 Hz,1 H) 8.22 (d, J=6. 11 Hz, 1 H) 8.32 (d, J=9. 29 Hz,1 H) 8.35 (d, J=6. 11 Hz,1 H).

References: [1]Patent: WO2003/99274,2003,A1 .Location in patent: Page 286-287.
[2]Patent: WO2003/99274,2003,A1 .Location in patent: Page 288.

10
[ 214045-86-0 ]
[ 123324-71-0 ]
[ 1372215-45-6 ]

References: [1]Journal of Materials Chemistry,2012,vol. 22,p. 8399 - 8407.

11
[ 214045-86-0 ]
[ 172975-69-8 ]
[ 1372215-46-7 ]

References: [1]Journal of Materials Chemistry,2012,vol. 22,p. 8399 - 8407.

12
[ 1372215-44-5 ]
[ 214045-86-0 ]

References: [1]Journal of Materials Chemistry,2012,vol. 22,p. 8399 - 8407.

13
[ 214045-86-0 ]
1-amino-6-fluoro-isoquinoline [ No CAS ]