[ CAS No. 6624-49-3 ] {[proInfo.proName]}

Name: 6624-49-3|Isoquinoline-3-carboxylic acid|97%
Brand: Ambeed
SKU: A178875
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Quality Control of [ 6624-49-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 6624-49-3 ]

CAS No. :	6624-49-3	MDL No. :	MFCD00075137
Formula :	C₁₀H₇NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KVMMIDQDXZOPAB-UHFFFAOYSA-N
M.W :	173.17	Pubchem ID :	124656
Synonyms :

Calculated chemistry of [ 6624-49-3 ] Expand+

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	10
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	1.0
Molar Refractivity :	48.7
TPSA :	50.19 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.96 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.23
Log Po/w (XLOGP3) :	1.96
Log Po/w (WLOGP) :	1.93
Log Po/w (MLOGP) :	-0.03
Log Po/w (SILICOS-IT) :	1.82
Consensus Log Po/w :	1.38

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-2.65
Solubility :	0.386 mg/ml ; 0.00223 mol/l
Class :	Soluble
Log S (Ali) :	-2.64
Solubility :	0.398 mg/ml ; 0.0023 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.07
Solubility :	0.147 mg/ml ; 0.000851 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.21

Safety of [ 6624-49-3 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 6624-49-3 ]

* 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.

Upstream synthesis route of [ 6624-49-3 ]
Downstream synthetic route of [ 6624-49-3 ]

[ 6624-49-3 ] Synthesis Path-Upstream 1~14

1
[ 6624-49-3 ]
[ 25475-67-6 ]

Reference： [1] Journal of the American Chemical Society, 1951, vol. 73, p. 688

2
[ 74163-81-8 ]
[ 6624-49-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium permanganate In N,N-dimethyl-formamide at 0 - 20℃; for 100.5 h; Inert atmosphere	At 0 °C to a solution of 10.0 g (0.046 mmol) of (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid in 200 ml of N,N-dimethylformamide 5.0 g (0.032 mmol) of KMnO₄ was added, which took 30 min. The reaction mixture was stirred at room temperature for 100 h, and TLC (CCl₃:CH₃OH = 5:1) indicated the complete disappearance of (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid. The reaction mixture was evaporated under vacuum. The residue was washed with distilled water repeatedly to provide 8.1 g (83percent) of the title compound as a yellow powder. ESI-MS (m/e) 174 [M + H]⁺; ¹H NMR (300 MHz, DMSO) δ/ppm = 10.81 (s, 1 H), 9.52 (s, 1 H), 8.43 (s, 1 H), 7.52 (m, 4 H); ¹³C NMR (75 MHz, DMSO) δ/ppm = 164.9, 152.3, 143.5, 136.2, 131.3, 129.7, 127.2, 125.8.

Reference： [1] European Journal of Medicinal Chemistry, 2011, vol. 46, # 5, p. 1672 - 1681
[2] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 20, p. 4434 - 4436
[3] Patent: CN106986825, 2017, A,
[4] Journal of Agricultural and Food Chemistry, 2018, vol. 66, # 34, p. 8957 - 8965

3
[ 27104-73-0 ]
[ 6624-49-3 ]

Yield	Reaction Conditions	Operation in experiment
60.69%	With sodium hydroxide In methanolCooling with ice	Add to 100ml eggplantIsoquinoline-3-carboxylate (3) (858 mg, 4.59 mmol)With a small amount of methanol dissolved, ice salt bath with 2N NaOH to adjust the pH = 12, a white precipitate;After the reaction is over,Ice salt bath with saturated KHSO4 adjusted pH = 7,Remove all solvents.The mixture was dissolved in a mixed solution of dichloromethane and methanol, and the filtrate was collected by filtration.After the filtrate was removed,A white solid (481.7 mg, 60.69percent) was obtained.

Reference： [1] Patent: CN106986825, 2017, A, . Location in patent: Paragraph 0023; 0033; 0034
[2] Patent: CN107137355, 2017, A, . Location in patent: Paragraph 0088; 0089
[3] Journal of Agricultural and Food Chemistry, 2018, vol. 66, # 34, p. 8957 - 8965

4
[ 67123-97-1 ]
[ 119-65-3 ]
[ 6624-49-3 ]

Reference： [1] Journal of the American Chemical Society, 1981, vol. 103, # 15, p. 4642 - 4643
[2] Journal of the American Chemical Society, 1981, vol. 103, # 15, p. 4642 - 4643

5
[ 1125-80-0 ]
[ 6624-49-3 ]

Reference： [1] Organic Process Research and Development, 2002, vol. 6, # 4, p. 477 - 481
[2] Justus Liebigs Annalen der Chemie, 1958, vol. 613, p. 153,155, 162

6
[ 63-91-2 ]
[ 6624-49-3 ]

Reference： [1] European Journal of Medicinal Chemistry, 2011, vol. 46, # 5, p. 1672 - 1681
[2] Patent: CN106986825, 2017, A,
[3] Patent: CN107137355, 2017, A,
[4] Journal of Agricultural and Food Chemistry, 2018, vol. 66, # 34, p. 8957 - 8965

7
[ 79815-19-3 ]
[ 6624-49-3 ]

Reference： [1] Patent: CN106986825, 2017, A,
[2] Journal of Agricultural and Food Chemistry, 2018, vol. 66, # 34, p. 8957 - 8965

8
[ 67123-97-1 ]
[ 6624-49-3 ]

Reference： [1] Patent: CN107137355, 2017, A,

9
[ 57060-86-3 ]
[ 6624-49-3 ]

Reference： [1] Patent: CN107137355, 2017, A,

10
[ 143468-70-6 ]
[ 6624-49-3 ]
[ 100-02-7 ]

Reference： [1] Tetrahedron Letters, 1992, vol. 33, # 29, p. 4191 - 4194

11
[ 6624-49-3 ]
[ 50458-77-0 ]

Reference： [1] Journal of the American Chemical Society, 1951, vol. 73, p. 688
[2] Journal of Organic Chemistry, 1958, vol. 23, p. 900
[3] Journal of Organic Chemistry, 1952, vol. 17, p. 471

12
[ 6624-49-3 ]
[ 64-17-5 ]
[ 50458-79-2 ]

Reference： [1] Journal of Organic Chemistry, 1952, vol. 17, p. 471
[2] Journal of the American Chemical Society, 2008, vol. 130, # 13, p. 4447 - 4458

13
[ 6624-49-3 ]
[ 67123-97-1 ]

Reference： [1] Journal of Medicinal Chemistry, 1993, vol. 36, # 3, p. 314 - 319

14
[ 67-56-1 ]
[ 6624-49-3 ]
[ 27104-73-0 ]

Yield	Reaction Conditions	Operation in experiment
75%	Reflux	The compound 3-isoquinolinecarboxylic acid (0801-132) (1.0 g, 5.78 mmol, 1.0 eq.)Dissolved in 30 ml of methanol,Sulfuric acid (0.5 ml) was then added and the reaction was refluxed overnight.After the reaction is finished, add sodium bicarbonate solutionpH to 8, extracted with dichloromethane, liquid-separated, and the organic phase dried over anhydrous sodium sulfate.Spin-drying afforded the compound 3-isoquinolinecarboxylic acid methyl ester (810 mg, 75percent).

Reference： [1] Patent: CN107383024, 2017, A, . Location in patent: Paragraph 0383

[ 6624-49-3 ] Synthesis Path-Downstream 1~109

2
[ 6624-49-3 ]
[ 50458-77-0 ]

Reference： [1]Journal of the American Chemical Society,1951,vol. 73,p. 688
[2]Journal of Organic Chemistry,1958,vol. 23,p. 900
[3]Journal of Organic Chemistry,1952,vol. 17,p. 471

3
[ 6624-49-3 ]
[ 103041-27-6 ]

Reference： [1]Chemistry - A European Journal,2014,vol. 20,p. 3610 - 3615
[2]Journal of Organic Chemistry,2015,vol. 80,p. 5919 - 5927
[3]Journal of Organic Chemistry,1958,vol. 23,p. 900

4
[ 6624-49-3 ]
[ 67123-97-1 ]

Reference： [1]Journal of Medicinal Chemistry,1993,vol. 36,p. 314 - 319

5
[ 67123-97-1 ]
[ 119-65-3 ]
[ 6624-49-3 ]

Reference： [1]Journal of the American Chemical Society,1981,vol. 103,p. 4642 - 4643
[2]Journal of the American Chemical Society,1981,vol. 103,p. 4642 - 4643

6
[ 143468-70-6 ]
[ 6624-49-3 ]
[ 100-02-7 ]

Reference： [1]Tetrahedron Letters,1992,vol. 33,p. 4191 - 4194

7
[ 873962-03-9 ]
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid {4-[2-(8-methoxy-1,2,4,4a,5,6-hexahydro-pyrazino[1,2-a]quinolin-3-yl)-ethyl]-cyclohexyl}-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 443 - 446

8
[ 444896-69-9 ]
[ 6624-49-3 ]
Isoquinoline-3-carboxylic acid ((R)-1-(4-chloro-benzyl)-2-{4-[2-diethylamino-1-(2-fluoro-phenyl)-ethyl]-piperazin-1-yl}-2-oxo-ethyl)-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 2341 - 2346

9
[ 6624-49-3 ]
[ 108-23-6 ]
C₁₄H₁₃NO₄ [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2006,vol. 54,p. 1010 - 1016

10
[ 929611-05-2 ]
[ 6624-49-3 ]
C₂₄H₂₄F₃N₇O₄ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 832 - 835

11
[ 6624-49-3 ]
[ 872171-14-7 ]
[ 872171-25-0 ]

Yield	Reaction Conditions	Operation in experiment
54%	With NMM; benzotriazol-1-ol; In N,N-dimethyl-formamide;	Example 156 A solution of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> (346 mg, 2.0 mmol), example Z (315 mg, 1.0 mmol), EDCI (394 mg, 2.0 mmol), HOBt (270 mg, 2.0 mmol), and NMM (1.0 mL) in DMF (10 mL) was stirred at RT overnight. After quenching with water (50 mL), the reaction mixture was extracted with ethyl acetate (3*100 mL). The combined organic extracts were washed with brine, dried (NaSO4) and filtered. After concentrated under reduced pressure, the residue was purified by flash chromatography to afford 3-(3-{3-t-butyl-5-[(isoquinoline-3-carbonyl)-amino]-pyrazol-1-yl}-phenyl)-propionic acid ethyl ester (250 mg, 54percent). 1H-NMR (CD3OD): 9.24 (s, 1H), 8.63 (s, 1H), 8.17 (d, J=8.0 Hz, 1H), 8.11 (d, J=8.0 Hz, 1H), 7.88 (t, J=7.6 Hz, 1H), 7.81 (t, J=7.6 Hz, 1H), 7.50 (s, 1H), 7.48 (d, J=7.6 Hz, 1H), 7.54 (d, J=7.6 Hz, 2H), 7.36 (d, J=7.6 Hz, 1H), 6.75 (s, 1H), 4.04 (q, J=7.6 Hz, 2H), 3.01 (t, J=7.6 Hz, 2H), 2.69 (t, J=7.6 Hz, 2H), 1.39 (s, 9H), 1.14 (t, J=7.6 Hz, 3H); MS (ESI) m/z: 471 (M+H+).

Reference： [1]Patent: US2005/288286,2005,A1

12
[ 6624-49-3 ]
ecteinascidin 770 6'-O-3''-isoquinolincarboxylate [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,2006,vol. 54,p. 1010 - 1016

13
[ 6624-49-3 ]
[ 682749-63-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1259 - 1263

14
[ 6624-49-3 ]
2-{4-[(isoquinoline-3-carbonyl)-amino]-1-methyl-1H-pyrrol-2-yl}-3H-benzoimidazole-5-carboxylic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1253 - 1257

15
[ 6624-49-3 ]
2-{4-[(isoquinoline-3-carbonyl)-amino]-1-methyl-1H-pyrrol-2-yl}-3H-benzoimidazole-5-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1253 - 1257

16
[ 6624-49-3 ]
1-(3-dimethylamino-propyl)-4-[(isoquinoline-3-carbonyl)-amino]-1H-pyrrole-2-carboxylic acid benzotriazol-1-yl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1259 - 1263

17
[ 6624-49-3 ]
2-{4-[(isoquinoline-3-carbonyl)-amino]-1-methyl-1H-pyrrol-2-yl}-3H-benzoimidazole-5-carboxylic acid benzotriazol-1-yl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1253 - 1257

18
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid {1-methyl-5-[6-(2-morpholin-4-yl-ethylcarbamoyl)-1H-benzoimidazol-2-yl]-1H-pyrrol-3-yl}-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1253 - 1257

19
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid [5-[5-(1H-benzoimidazol-2-yl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-(3-dimethylamino-propyl)-1H-pyrrol-3-yl]-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1259 - 1263

20
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid {1-(3-dimethylamino-propyl)-5-[5-(3H-imidazo[4,5-c]pyridin-2-yl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1H-pyrrol-3-yl}-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1259 - 1263

21
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid {1-(3-dimethylamino-propyl)-5-[5-(3H-imidazo[4,5-b]pyridin-2-yl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1H-pyrrol-3-yl}-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1259 - 1263

22
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid {1-(3-dimethylamino-propyl)-5-[1-methyl-5-(9H-purin-8-yl)-1H-pyrrol-3-ylcarbamoyl]-1H-pyrrol-3-yl}-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 1259 - 1263

23
[ 6624-49-3 ]
[ 600709-92-0 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3822 - 3839

24
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid {4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-butyl}-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3822 - 3839

25
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid {4-[4-(2,4-dichloro-phenyl)-piperazin-1-yl]-butyl}-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3822 - 3839

26
[ 6624-49-3 ]
[ 605658-34-2 ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

27
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (5-{5-[5-(3-dimethylamino-propylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

28
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (1-methyl-5-{1-methyl-5-[1-methyl-5-(4-methyl-piperazin-1-ylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl]-1H-pyrrol-3-ylcarbamoyl}-1H-pyrrol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

29
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (5-{5-[5-(3-dimethylamino-2,2-dimethyl-propylcarbamoyl)-1-methyl-1H-pyrrol-3-ylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

30
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (1-methyl-5-{1-methyl-5-[1-methyl-5-(2-pyrrolidin-1-yl-ethylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl]-1H-pyrrol-3-ylcarbamoyl}-1H-pyrrol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

31
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (1-methyl-5-{1-methyl-5-[1-methyl-5-(2-thiomorpholin-4-yl-ethylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl]-1H-pyrrol-3-ylcarbamoyl}-1H-pyrrol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

32
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (1-methyl-5-{1-methyl-5-[1-methyl-5-(2-piperidin-1-yl-ethylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl]-1H-pyrrol-3-ylcarbamoyl}-1H-pyrrol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

33
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (1-methyl-5-{1-methyl-5-[1-methyl-5-(2-piperazin-1-yl-ethylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl]-1H-pyrrol-3-ylcarbamoyl}-1H-pyrrol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

34
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid [5-(5-{5-[2-(4-fluoro-piperidin-1-yl)-ethylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-ylcarbamoyl)-1-methyl-1H-pyrrol-3-yl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

35
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (1-methyl-5-{1-methyl-5-[1-methyl-5-(3-piperidin-1-yl-propylcarbamoyl)-1H-pyrrol-3-ylcarbamoyl]-1H-pyrrol-3-ylcarbamoyl}-1H-pyrrol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

36
[ 6624-49-3 ]
4-hydroxy-1-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-(isoquinoline-3-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}piperidine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

37
[ 6624-49-3 ]
N-[1-methyl-5-([1-methyl-5-([1-methyl-5-([3-(4-morpholinyl)propyl]amino}carbonyl)-1H-pyrrol-3-yl]amino}carbonyl)-1H-pyrrol-3-yl]amino}carbonyl)-1H-pyrrol-3-yl]-3-isoquinolinecarboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

38
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid [5-(5-{5-[2-(4,4-difluoro-piperidin-1-yl)-ethylcarbamoyl]-1-methyl-1H-pyrrol-3-ylcarbamoyl}-1-methyl-1H-pyrrol-3-ylcarbamoyl)-1-methyl-1H-pyrrol-3-yl]-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2003,vol. 46,p. 3914 - 3929

39
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (4-oxo-1-phenyl-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 4850 - 4867

40
[ 6624-49-3 ]
isoquinoline-3-carboxylic acid (9-methyl-4-oxo-1-phenyl-3,4,6,7-tetrahydro-[1,4]diazepino[6,7,1-hi]indol-3-yl)-amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 4850 - 4867

41
[ 6624-49-3 ]
(3R)-Isoquinoline-3-carboxylic acid (9-methoxy-4-oxo-1-phenyl-3,4,6,7-tetrahydro[1,4]diazepino-[6,7,1-hi]indol-3-yl)amide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2000,vol. 43,p. 4850 - 4867

42
[ 6624-49-3 ]
[ 176685-43-1 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 1448 - 1458

43
[ 6624-49-3 ]
[ 157822-74-7 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 1448 - 1458

44
[ 6624-49-3 ]
[ 157904-29-5 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 1448 - 1458

45
[ 6624-49-3 ]
8-chloromethyl-6-{5-[(isoquinoline-3-carbonyl)-amino]-1H-indole-2-carbonyl}-4-(4-nitro-phenoxycarbonyloxy)-2-trifluoromethyl-3,6,7,8-tetrahydro-3,6-diaza-as-indacene-1-carboxylic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 1448 - 1458

46
[ 6624-49-3 ]
methyl (1S)-1-chloromethyl-3-[5-[(isoquinolin-3-ylcarbonyl)amino]-1H-indol-2-ylcarbonyl]-5-(4-methylpiperazin-1-ylcarbonyl)oxy-7-trifluoromethyl-1,2,3,6-tetrahydropyrrolo[3,2-e]indole-8-carboxylate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 1448 - 1458

47
[ 6624-49-3 ]
[ 139040-51-0 ]
C₂₆H₂₂N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide);	[3-BIPHENYL-4-YL-(2S)-[(ISOQUINOLINE-3-CARBONYL)-AMINO]-PROPIONIC ACID] 2-L-amino-3-biphenyl-4-yl-propionic acid methyl ester (100 mg, 0.1 [MMOL)] was reacted with <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> (78 mg, 0.5 [MMOL)] as described in general procedure A. The resulting compound was hydrolyzed according to general procedure C to afford the title product (132 mg, 81 percent) as a white solid.

Reference： [1]Patent: WO2004/14844,2004,A2 .Location in patent: Page 179; 183

48
[ 548773-04-2 ]
[ 6624-49-3 ]
3-[[4-[4-[(4-bromophenyl)(ethoxyimino)methyl]-1-piperidinyl]-4-methyl-1-piperidinyl]carbonyl]isoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; HATU; In DMF (N,N-dimethyl-formamide); at 20℃; for 16h;	To a solution OF OXIME-AMINE, 4- [ (4-BROMOPHENYL) (ethoxyimino) methyl]-1-(4-methyl-4- piperidinyl) piperidine (50 mg, 0.12 MMOL), <strong>[6624-49-3]3-isoquinolinecarboxylic acid</strong> (25 mg, 0.14 MMOL), and Et3N (44 mg, 0.43 MMOL) in DMF (3mL, anhydrous) was added HATU (60mg, 0. 16MMOL) at room temperature. Atter 16 h the reaction mixture was poured into ice water. The solid was collected by filtration, and RE-DISSOLVED in CH2CI2. The organic phase was dried over NA2SO4, and concentrated in vacuo. The residue was purified by preparative TLC (CH2CI2-MeOH, 9: 1) to afford the title compound as a light yellow powder. MS: 564 (M++1).

Reference： [1]Patent: WO2004/113323,2004,A1 .Location in patent: Page 33; 34

49
[ 6624-49-3 ]
[ 851882-63-8 ]
{(S)-3-[3-(4-fluoro-phenyl)-1,2,4-oxadiazol-5-yl]-piperidin-1-yl}-isoquinolin-3-yl-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With 1-hydroxy-7-aza-benzotriazole; PS-DCC; N-ethyl-N,N-diisopropylamine; In dichloromethane;	Example 43 { (S)-3- [3- (4-Fluoro-phenyl)-l, 2, 4-oxadiazol-5-yl]-piperidin-1-yl}-isoquinolin-3-yl- methanone The compound was prepared following the procedure described in the Example 36, using <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> as the acid of choice and S-3- [3- (4-fluoro- phenyl)- [1, 2,4] oxadiazol-5-yl] -piperidine hydrochloride (prepared as described in the Example 12). Yield : 56percent (white oil); [a] D20 = +150° (c=0.8, CHCl3) ; LCMS (Tr): 5.59 min (Method A); MS (ES+) gave m/z : 403.2. 1H-NMR (CDC13, 333K, 300 MHz), 8 (ppm): 8.23 (d, 1H); 8.12 (d, 1H); 8.02 (m br, 2H); 7. 84 (d, 1H) ; 7.76 (d, 1H); 7.74 (m, 1H) ; 7.59 (dd, 1H); 7.13 (dd br, 2H); 5.01, 4.51 and 4. 18 (m br, 2H); 3.77-3. 26 (m br, 3H); 2.39 (m, 1H); 2.18-1. 78 (m br, 3H).

Reference： [1]Patent: WO2005/44797,2005,A1 .Location in patent: Page/Page column 76

50
[ 6624-49-3 ]
[ 1117-97-1 ]
[ 362057-20-3 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; In dichloromethane; for 18h;Product distribution / selectivity;	Step 1: Isoquinoline-3-carboxylic acid methoxy-methyl-amide 2.46 g (12.9 mmol) of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> hydrate was dissolved in 100 mL dichloromethane under room temperature. 1.38 g (14.1 mmol) of methoxymethyl amine was added followed by addition of 4.55 g (15.5 mmol) of 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride and 1.44 g (14.1 mmol) of triethylamine. The reaction was stirred for 18 hour and 250 ml of water was added. The organic layer was dried over anhydrous magnesium sulfate and evaporated in vacuum. Purification using flash chromatography, elution with 100percent ethyl acetate yielded to 2.70 g of product as colorless solid. LC-MSD, m/z for C14H25NO3 [M+H]+: 217.3, [M+2H]+: 218.3. LC retention time on HPLC, C18 column gradient 20-95percent acetonitrile with 0.1percent TFA in 4 min: 0.492 min.

Reference： [1]Patent: US2006/74071,2006,A1 .Location in patent: Page/Page column 32

51
[ 6624-49-3 ]
[ 6638-79-5 ]
[ 362057-20-3 ]

Yield	Reaction Conditions	Operation in experiment
67%	With N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine; In dichloromethane; at 20℃; for 3h;	Example 1 Production of N-benzyl-2-[3-benzyl-3,4-dihydroisoquinolin-2(1H)-yl]ethanamine a) Production of N-methoxy-N-methylisoquinoline-3-carboxyamide [Show Image]; 200 mg of <strong>[6624-49-3]3-isoquinolinecarboxylic acid</strong>, 169 mg of N,O-dimethylhydroxylamine monohydrochloride, 332 mg of WSC, and 582 mg of triethylamine were dissolved in 2 mL of dichloromethane, followed by stirring at room temperature for 3 hours. Water was added to the reaction liquid, followed by extraction with chloroform. The organic layer was then washed with saturated brine, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The residue obtained was purified using silica gel chromatography (chloroform alone) to obtain 169 mg (yield 67percent) of a title compound as a pale yellow solidified product. 1H-NMR (CDCl3) delta: 3.47 (3H, s), 3.80 (3H, s), 7.69 (1H, ddd, J = 1.2, 8.0, 8.0 Hz), 7.76 (1H, ddd, J =1.2, 8.0, 8.0 Hz), 7.92 (1H, d, J = 8.0 Hz), 8.02 (1H, d, J = 8.0 Hz), 8.14 (1H, s), 9.25 (1H, s).
	With triethylamine; 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; In acetonitrile; for 48h;Product distribution / selectivity;	Step 1: Isoquinoline-3-carboxylic acid methoxy-methyl-amide In 50 mL of acetonitrile was dissolved 0.49 g (2.60 mmol) of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> monohydrate. To this 0.28 g (2.87 mmol) of O,N-dimethyl-hydroxylamine hydrochloride, 0.4 mL (2.87 mmol) triethylamine and 0.921 g (3.13 mmol) of 4-(4,6-dimethoxy-[1,3,5]triazin-2-yl)-4-methyl-morpholin-4-ium chloride hydrate were added and stirred for 2 days and then evaporated. A mixture of dichloromethane and water was added to it and the organic layer was evaporated and purified using flash chromatography (0-20percent methanol in dichloromethane). Fractions containing pure product were evaporated to yield 210 mg of the free base as a white solid. LC-MSD, m/z for C12H12N2O2 [M+H]+: 217.4, [M+Na]+: 239.4

Reference： [1]Patent: EP2143714,2010,A1 .Location in patent: Page/Page column 24-25
[2]Patent: US2006/74071,2006,A1 .Location in patent: Page/Page column 48

52
[ 6624-49-3 ]
[ 100959-19-1 ]
[ 530-62-1 ]
[ 311346-55-1 ]

Yield	Reaction Conditions	Operation in experiment
377 mg (70%)	With N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide;	Example 18 Preparation of N-(trans-4-methylcyclohexyl)isoquinoline-3-carboxamide (406) A solution of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> (346 mg, 2 mmol), and 1,1'-carbonyldiimidazole (325 mg, 2 mmol) in dimethylformamide (4 mL) was heated at 50° C. for 1 hour. After this time, trans-4-methylcyclohexylamine hydrochloride (300 mg, 2 mmol), and N,N-diisopropylethylamine (0.523 mL, 3 mmol) were added and the mixture heated at 50° C. for 16 hours. The reaction mixture was cooled, and diluted with ethyl acetate (20 mL). The organic solution was washed with water (3*15 mL), brine (20 mL), dried over anhydrous MgSO4, filtered and concentrated to afford 377 mg (70percent) of 406: rt=9.65 min.; m/z (rel. int.) 268 (M+, 9), 240 (6), 223 (16), 211 (17), 197 (13), 173 (22), 156 (55), 128 (100), 112 (38), 101 (15), 77 (10).

Reference： [1]Patent: US6429207,2002,B1

53
[ 6624-49-3 ]
[ 960358-70-7 ]
N-[3-(8-(2,6-difluorophenyl)-2-[2-hydroxy-1-(hydroxymethyl)ethyl]amino}-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl)-4-methylphenyl]-3-isoquinolinecarboxamide trifluoacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide;	37b) iV-r3-(8-(2.6-difluorophenylV2-([2-hydroxy-l-(hvdroxynietlivpietliyllanimol- 7-QXQ-7, 8-dihvdropyrido [2,3 -^pyrimidin-4- yl)-4-methylphenyl] -3 - isoquinolinecarboxamide trifluoroacetateTo <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> (11.5 mg, 0.066 mmol, 1 eq) was added HATU (38.02 mg, 0.1 mmol, 1.5 eq) in DMF (250 uL). DIPEA (34.84 uL, 0.2 mmol, 3 eq) was then added. The resulting mixture was then allowed to stand for about 5 minutes before 4-(5-amino-2-methyl-phenyl)-8-(2,6-difluoro-phenyl)-2-(2- hydroxy- 1 -hydroxymethyl-ethylamino)-8H-pyrido[2,3 -d]pyrimidin-7-one (30.23 mg, 0.066 mmol, 1 eq) was added. The resulting mixture was shaken to ensure efficient mixing of the reagents then was left to stand overnight. The solvent was then removed in vacuo. The residue was dissolved in methanol and was then placed down an aminopropyl SPE flushing the column with methanol. The elute from the SPE was then treated with NaOH (2 M, 200 uL) and the mixture was allowed to stand for about 1 hr. This was followed by HCl (2M, 200 uL) then the solvent was removed in vacuo. The residue was purified by MDAP. LC-MS m/z 609 (M+H)+, 3.31 min (ret time). EPO <DP n="158"/>

Reference： [1]Patent: WO2006/104915,2006,A2 .Location in patent: Page/Page column 156

54
[ 6624-49-3 ]
[ 165454-13-7 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In toluene; at 0 - 50℃; for 0.833333h;	To a solution of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> (0.200, g, 1.155 mmol) in anhydrous toluene (3 mL) cooled to 0 C., is added 253 mL of thionyl chloride, and the mixture is stirred for 20 minutes. The temperature is increased to 50 C. and the mixture is stirred for additional 30 minutes until the formation of white solid in the mixture. It is then cooled and the solvents are removed in vacuo, followed by the addition of toluene (2*3 mL) and their removal in vacuo. Fresh toluene (3 mL) is then added to the mixture and it is cooled to 0 C. To the mixture is added Huenig's base (502 muL, 2.89 mmol) followed by the addition of amine (0.343 g, 1.39 mmol) and stirred for half an hour. The reaction mixture is allowed to warm to room temperature and is stirred for another 2 hours. To the reaction is added 10 mL of water followed by the addition of HCl (4 mL, 1 N). The layers are separated and the aqueous layer is washed with toluene and the combined organic fractions are washed with water (10 mL), brine (10 mL), and dried over sodium sulfate. Toluene is decanted and filtered through silica gel using toluene (40 mL). The resulting solution is evaporated and dissolved in (dichloromethane, 8 mL), washed with saturated sodium carbonate (15 mL), dried by passing through silica plug, and eluding with dichloromethane. The solvents are removed in vacuo, to provide desired product (0.290 g, 62.5%). LCMS: 403.00 (M+H+).
	With thionyl chloride; for 1h;Heating / reflux;	5.109 ISOQUINOLINE-3-CARBOXYLIC ACID [2-(2,6-DIOXOPIPERIDIN-3-YL)-1,3-DIOXO-2,3-DIHYDRO-1H-ISOINDOL-4-YLMETHYL]AMIDE A mixture of isoquinoline 3-carboxylic acid (0.39 g, 2.0 mmol) and thionyl chloride (10 mL) was heated to reflux for 1 hour. Excess thionyl chloride was removed under vacuum. To the acid chloride, was then added 4-aminomethyl-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione hydrochloride (0.65 g, 2.0 mmol), THF (30 mL) and triethylamine (0.61 g, 6.0 mmol), and the resulting mixture was stirred at reflux for 90 minutes. The solvent was evaporated and the crude residue was chromatographed using a methylene chloride-methanol gradient, eluting 0.67 g of the product with 96:4 methylene chloride-methanol, in 76% yield: mp 198-200 C.; 1H NMR (DMSO-d6) delta 2.07-2.11 (m, 1H), 2.53-2.66 (m, 2H), 2.85-2.97 (m, 1H), 5.02 (d, J=6.3 Hz, 2H), 5.19 (dd, J=12.6 Hz, d=5.3 Hz, 1H), 7.71-7.92 (m, 5H), 8.21 (d, J=7.8 Hz, 1H), 8.28 (d, J=7.8 Hz, 1H) 8.59 (s, 1H), 9.43 (s, 1H), 9.65 (t, J=6.3 Hz, 1H), 11.17 (s, 1H); 13C NMR (DMSO-d6) delta 22.0, 31.0, 38.5, 48.9, 120.0, 121.9, 127.2, 127.8, 128.0, 129.2, 129.3, 131.4, 131.6, 133.0, 134.8, 135.4, 139.2, 143.4, 151.7, 164.7, 167.0, 167.6, 169.9, 172.8; Anal. calcd for C24H18N4O5.0.5H2O: C, 63.85; H, 4.24; N, 12.41. Found: C, 63.85; H, 3.93; N, 12.31.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; for 2h;	Oxalyl chloride (91 muL, 1.04 mmol, 1.8 eq) was added dropwise to a mixture of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> (100 mg, 0.58 mmol, 1.0 eq) and DMF (5 muL, 0.06 mmol, 0.1 eq) in DCM (1.7 mL). The reaction was stirred for 2 hrs. The reaction was concentrated under reduced pressure to give a yellow residue of isoquinoline-3-carbonyl chloride, which was used in the next step without purification.

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 3453 - 3456
[2]Patent: US2006/276515,2006,A1 .Location in patent: Page/Page column 44
[3]Patent: US2007/49618,2007,A1 .Location in patent: Page/Page column 113
[4]Journal of Medicinal Chemistry,2012,vol. 55,p. 9589 - 9606
[5]Organic Letters,2014,vol. 16,p. 3142 - 3145
[6]Patent: WO2018/218042,2018,A1 .Location in patent: Page/Page column 72
[7]Journal of the American Chemical Society,2018,vol. 140,p. 11487 - 11494

55
[ 6624-49-3 ]
[ 919093-81-5 ]
C₃₅H₄₄N₆O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With N-ethyl-N,N-diisopropylamine; ((3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V); In acetonitrile;	Following the general procedure of acid-amine coupling as shown in Example 23, Compound 8 (25 mg, 0.033 mmol) was treated with <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> hydrate (8.6 mg, 0.045 mmol), DIEA (0.0163 mL, 0.094 mmol) and the coupling reagent PyAOP (29.3 mg, 0.056 mmol) in acetonitrile (3 mL). After purification by Prep.HPLC column, a white solid as TFA salt was obtained as final 1:1 diastereomers (Compound 28) (19.9 mg, 66percent yield). (Compound 28, 48110-188A): 1H NMR(CD3OD, 500 MHz) delta:9.37 (s, 1H), 8.65 (s, 1H), 8.26 (d, J=8.2 Hz, 1H), 8.14 (d, J=8.2 Hz, 1H), 7.95 (t, J=7.6 Hz, 1H), 7.87t, J=7.6 Hz, 1H), 5.75 (m, 1H), 5.32 (m, 1H), 5.14 (m, 1H), 4.84 (m, 1H), 4.63 (m, 1H), 4.50 (m, 1H), 4.08-4.18 (m, 2H), 2.95 (m, 1H), 2.43 (m, 1H), 2.1-2.36 (m, 4H), 1.90 (dd, J=7.9 Hz, 5.8 Hz, 0.5H), 1.82 (dd, J=7.9 Hz, 5.2 Hz, 0.5H), 1.43 (m, 1 H), 1.01-1.32 (m, 13H), 0.97 (m, 1H), 0.49 (m, 2H), 0.17 (m, 2H). LC-MS (retention time: 1.573 minutes.), MS m/z 693(MH+).

Reference： [1]Patent: US2007/10455,2007,A1 .Location in patent: Page/Page column 58

56
[ 6624-49-3 ]
[ 1239987-61-1 ]
[ 1057111-58-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 1h;	Step H; Isoquinoline-3-carboxylic acid 2-(3-isobutyrylamino-5-methoxycarbonyl-phenyl)-2-oxo-ethyl ester To a solution of N-[3-(2-bromo-acetyl)-5-propionyl-phenyl]-isobutyramide (Fw 395, 4 g, 10 mmol) in dry DMF (25 mL) was added of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> monohydrate (2.5 g, 13 mmol) and DIEA (5 mL) subsequently. The reaction mixture was stirred at rt for 1 h and then diluted with 150 mL of EtOAc, the organic phase was washed with 5percent NaHCO3 aq., dried over Na2SO4 and concentrated to afford the keto-ester was used directly in the next step.

Reference： [1]Patent: US2007/219239,2007,A1 .Location in patent: Page/Page column 35

57
[ 6624-49-3 ]
[ 1030927-60-6 ]
[ 1000276-76-5 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 6116 - 6125

58
[ 6624-49-3 ]
[ 1017956-55-6 ]
[ 1000276-81-2 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 6116 - 6125

59
[ 6624-49-3 ]
C₂₁H₃₄N₆O₂ [ No CAS ]
[ 1000276-80-1 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 6116 - 6125

60
[ 6624-49-3 ]
[ 1030927-06-0 ]
[ 1000276-67-4 ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 6116 - 6125

61
[ 67-56-1 ]
[ 6624-49-3 ]
nickel(II) chloride hexahydrate [ No CAS ]
[ 769163-83-9 ]

Reference： [1]Acta Crystallographica, Section C: Crystal Structure Communications,2004,vol. 60,p. m345-m347

62
[ 6624-49-3 ]
[ 1131-16-4 ]
iridium(III) chloride hydrate [ No CAS ]
[ 850421-83-9 ]

Reference： [1]Organometallics,2005,vol. 24,p. 1578 - 1585

63
[ 20518-17-6 ]
[ 6624-49-3 ]
iridium(III) chloride hydrate [ No CAS ]
[(1-isoquinolinecarboxylate)Ir(MeC₆H₃C₃H₃N₂)2]*H₂O [ No CAS ]

Reference： [1]Organometallics,2005,vol. 24,p. 1578 - 1585

64
[ 850380-23-3 ]
[ 6624-49-3 ]
iridium(III) chloride hydrate [ No CAS ]
[(isoquinolinecarboxylate)Ir(MeC₆H₃C₃H₃N₂)2]*H₂O [ No CAS ]

Reference： [1]Organometallics,2005,vol. 24,p. 1578 - 1585

65
[ 14766-43-9 ]
[ 6624-49-3 ]
iridium(III) chloride hydrate [ No CAS ]
[(3-isoquinolinecarboxylate)Ir(C₆H₄C₃H₂(Me)N₂)2] [ No CAS ]

Reference： [1]Organometallics,2005,vol. 24,p. 1578 - 1585

66
[ 6624-49-3 ]
iridium(III) chloride hydrate [ No CAS ]
[ 850380-24-4 ]
[(3-isoquinolinecarboxylate)Ir(MeC₆H₃C₃H₂(CH₃)2N₂)2]*0.5H₂O [ No CAS ]

Reference： [1]Organometallics,2005,vol. 24,p. 1578 - 1585

67
[ 6624-49-3 ]
iridium(III) chloride hydrate [ No CAS ]
[ 1126-00-7 ]
[(1-isoquinolinecarboxylate)Ir(phenylpyrazole(-1H))2]*H₂O [ No CAS ]

Reference： [1]Organometallics,2005,vol. 24,p. 1578 - 1585

68
[ 67-56-1 ]
[ 6624-49-3 ]
copper(II) choride dihydrate [ No CAS ]
[ 769163-84-0 ]

Reference： [1]Acta Crystallographica, Section C: Crystal Structure Communications,2004,vol. 60,p. m345-m347

69
[ 67-56-1 ]
[ 6624-49-3 ]
nickel(II) nitrate hexahydrate [ No CAS ]
[ 769163-83-9 ]

Reference： [1]Inorganica Chimica Acta,2007,vol. 360,p. 3442 - 3447

70
[ 67-56-1 ]
[ 6624-49-3 ]
cobalt(II) chloride hexahydrate [ No CAS ]
[ 769163-82-8 ]

Reference： [1]Acta Crystallographica, Section C: Crystal Structure Communications,2004,vol. 60,p. m345-m347

71
[ 6624-49-3 ]
copper nitrate hemi(pentahydrate) [ No CAS ]
[ 7732-18-5 ]
copper(II)(μ-isoquinoline-3-carboxylate)(tetraaqua) [ No CAS ]

Reference： [1]Inorganica Chimica Acta,2007,vol. 360,p. 3442 - 3447

72
[ 6624-49-3 ]
zinc(II) nitrate hexahydrate [ No CAS ]
zinc(II)(μ-isoquinoline-3-carboxylate)(diaqua) [ No CAS ]

Reference： [1]Inorganica Chimica Acta,2007,vol. 360,p. 3442 - 3447

73
[ 6624-49-3 ]
[ 67025-97-2 ]
C₄₀H₃₆N₄O₅ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 1416 - 1427

74
[ 6624-49-3 ]
[ 67025-97-2 ]
C₄₀H₃₆N₄O₅ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 1416 - 1427

75
[ 6624-49-3 ]
[ 824-94-2 ]
[ 1369966-50-6 ]

Yield	Reaction Conditions	Operation in experiment
		Sodium hydride (2.78g, 69MMOL ; 60percent dispersion in oil) was added portionwise to a solution of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> (4.5g, 21MMOL) in DMF (90MOL) at room temperature under argon. After LH, 4-methoxybenzyl chloride (6.9g, 44MMOL) was added and the mixture stirred for 72h before being evaporated in vacuo and the residue partitioned between water and ethyl acetate. The organic phase was washed with brine, dried and concentrated in vacuo to give 4-methoxybenzyl 2- (4-methoxy-benzyl)-1, 2,3, 4-TETRAHYDRO- isoquinoline-3-carboxylate (9.7g) as a yellow oil used without further purification. The crude ester was heated at 100°C in a mixture OF DIOXAN (70ML) and 2M NAOH (70ML) for 16h and then cooled to room temperature. After a further 24h the reaction mixture was evaporated in vacuo and the residue partitioned between water and ethyl acetate. The aqueous phase was acidified with C. HCl and extracted with ethyl acetate. The combined extracts were dried and evaporated in vacuo to afford the title product (2.7g, 43percent) as a yellow SOLID.APOS;H NNM (DMSO) 5 : 3.13 and 3.27 (2H, ABq, higher field arm, d, J = 16 and 4 HZ ; lower field arm, d, J = 16 and 6Hz), 3.76 (3H, s), 3.95-4. 16 (5H, M), 6.95 (2H, d, J = 8Hz), 7.10-7. 20 (4H, M), 7.37 (2H, d, J = 8Hz), 11. 0 (1H, br s).

Reference： [1]Patent: WO2004/41816,2004,A1 .Location in patent: Page 14

76
[ 6624-49-3 ]
[ 6530-09-2 ]
isoquinoline-3-carboxylic acid {(S)-1-azabicyclo[2.2.2]oct-2-yl}-amide monohydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		529 mg of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> hydrate are dissolved in 18 mi of DMF, followed by addition of 508 mg of 1-hydroxy-benzotriazol and 1.81 G of dicyclohexyl-carbodiimide. After stirring for 1 h at r. t. , the precipitated dicylohexyl-urea is filtered off and 500 mg of 3 (S)- aminoquinuclidine dihydrochloride and 1.3 ml of ethyl-diisopropylamine is added to the filtrate. After stirring for 48 h at room temperature, a second portion of dicylohexyl-urea is filtered off and washed with MeOtBu/DMF (4: 1). Wash solution and filtrate are combined and crystallized by standing over night at 5° The crystalline precipitate is filtered off and washed with MeOtBu/DMF (4: 1), followed by MeOtBu to yield the title compound as monohydrochloride. NMR (1H, 400 MHz, AH d6-DMSO) : 1.75 (1H, t), 1.96 (2H, m), 2.12 (1H, q), 2.24 (1H, d), 3.24 (3H, m), 3.43 (2H, m), 3.65 (1'H, t), 4.49 (1H, q), 7. 86 (1H, t), 7.92 (1H, t), 8. 24 (1H, d), 8.30 (1H, d), 8. 61 (1H, s), 9.31 (1 H, d), 9. 46 (1H, s), 10.59 1H, br). MS (ES+) : 282 (MH)+

Reference： [1]Patent: WO2004/99206,2004,A1 .Location in patent: Page 6

77
[ 6624-49-3 ]
[ 852668-37-2 ]
[ 852668-48-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 5182 - 5185

78
[ 6624-49-3 ]
[ 459-73-4 ]
[ 1236037-48-1 ]

Reference： [1]Patent: WO2010/83384,2010,A2 .Location in patent: Page/Page column 65

79
[ 6624-49-3 ]
[ 67025-97-2 ]
NAQ dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%		17-CyclopropyImethyI-3,14beta-dihydroxy-4,5alpha-epoxy-6alpha-((3'- isoquinolyl)acetamido]morphinan (9, NAQ) was prepared by following the general procedure2 in 70percent yield. [alpha]25D: -150° (c=0.01 , MeOH). M.p.: 210-2130C; IR (KBr, cm"1) vmax: 3222, 1666, 1529, 1261 , 801 ; 1H NMR (300MHz, DMSO): delta 9.44(s, 1 H, Ar-H), 8.95(b, 1 H, exchangeable), 8.64(s, 1 H, Ar-H), 8.58(b, 1 H, Amide-H), 8.27(m, 2 H, Ar-H), 7.90(m, 2 H, Ar-H), 6.79 and 6.62(2 d, 1 H each, J= 7.8Hz, Ci-H, C2-H ), 4.8 l(s, 1 H, C5-H), 4.74(m, 1 H, C6-H), 3.99(m, 1 H), 3.45(m, 2 H), 3.14(m, 2 H), 2.73(m, 1 H), 2.58(m, 1 H), 2.23(m, 2 H), 1.87(m, 1 H),1.67(m, 2 H), 1.48(m, 1 H), 1.08(m, 1 H), 0.67(m, 2 H), 0.47(m, 2 H); 13C NMR (75MHz, DMSO) delta: 159.97, 148.87, 146.15, 139.18, 138.21, 137.40, 134.48, 132.47, 131.01 , 128.93, 128.86, 128.37, 124.16, 122.44, 120.07, 118.39, 87.91 , 69.86, 62.26, 57.93, 47.15, 46.05, 30.51, 29.43, 23.88, 19.57, 19.56, 5.75, 5.18, 2.26; MS (ESI) tn/z: 498.1 (M+H)+. Anal. (C30H31N3O4 2HCI O.5H2O) C, H.

Reference： [1]Patent: WO2010/83384,2010,A2 .Location in patent: Page/Page column 48-49

80
[ 6624-49-3 ]
[ 1158975-01-9 ]
[ 1254364-25-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 5839 - 5842

81
[ 6624-49-3 ]
2-amino-1-benzyl-1H-benzoimidazole-4-carboxylic acid methyl ester [ No CAS ]
1-benzyl-2-[(isoquinoline-3-carbonyl)-amino]-1H-benzoimidazole-4-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%		To a solution of 0.031 g (0.18 mmol) of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> in DMF (1 mL) was added 0.085 g (0.22 mmol) of HBTU and 0.1 mL of DIEA. The mixture was stirred for 5 min, then added 0.04 g (0.18 mmol) of 2-amino-l -benzyl- lH-benzoimidazole-4-carboxylic acid methyl ester in one portion. The reaction mixture was stirred for 1 h. After usual workup, EPO <DP n="164"/>45 mg (73percent) of l-benzyl-2-[(isoquinoline-3-carbonyl)-amino]-lH-benzoimidazole-4- carboxylic acid methyl ester was isolated after purification by column chromatography eluting with DCM/methanol (v/v from 15:1 to 10:1). LCMS: 437 (M + I)+; 1H NMR (DMSOd6, 400 MHz): delta 12.8 (s, IH), 9.41 (s, IH), 8.92(s, IH), 8.20 (d, IH), 8.14 (d, IH), 7.84 (t, IH), 7.77 (m, 3H), 7.51 (d, 2H), 7.32 (m, 4H), 5.63 (s, 2H), 3.99 (s, 3H) ppm.

Reference： [1]Patent: WO2006/99379,2006,A2 .Location in patent: Page/Page column 162-163

82
[ 6624-49-3 ]
[ 950225-69-1 ]
isoquinoline-3-carboxylic acid 2-{3-[(R)-1-(4-fluoro-phenyl)-ethylcarbamoyl]-5-nitro-phenyl}-2-oxo-ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A mixture of <strong>[6624-49-3]isoquinoline-3-carboxylic acid</strong> monohydrate (63 g, 0.364 mol) and Na2SO4 (10 g) in dry DMF (200 mL) was treated with DIEA (76 mL, 0.44 mol). The reaction mixture was stirred at rt for 20 min and cooled to 0° C. followed by drop wise addition of Intermediate 17 (147 g, 0.36 mol) in DMF (200 ml). The mixture was stirred for 2 h at 0° C. and then diluted with ice water and filtered. The collected solid was washed with water then dissolved in EtOAc. The organic phase was washed with saturated aqueous NaHCO3, then water, dried over Na2SO4 and concentrated. Hexane trituration afforded Intermediate 18 (155 g) (Isoquinoline-3-carboxylic acid 2-{3-[(R)-1-(4-fluoro-phenyl)-ethylcarbamoyl]-5-nitro-phenyl}-2-oxo-ethyl ester) as a white solid. 1H NMR (CDCl3): delta 9.34(1H), 8.68(1H), 8.08(2H), 8.01(1H), 7.80(2H), 7.75 (2H), 7.36(2H), 7.04(2H), 6.72(1H), 5.70(2H), 5.32(1H), 1.61(3H) ppm. LC/MS: m/z 503 (M+2)+

Reference： [1]Patent: US2007/219239,2007,A1 .Location in patent: Page/Page column 45

83
[ 6624-49-3 ]
vanadyl sulfate trihydrate [ No CAS ]
cis-[VO(3-isoquinolinecarboxylate)2(H₂O)] [ No CAS ]

Reference： [1]Inorganic Chemistry,2011,vol. 50,p. 883 - 899

84
[ 6624-49-3 ]
[ 51837-85-5 ]
[ 1266676-95-2 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 1010 - 1021

85
[ 6624-49-3 ]
[ 17831-01-5 ]
[ 1184612-28-9 ]