[ CAS No. 142327-44-4 ] {[proInfo.proName]}

Name: 142327-44-4|Methyl 2-(3-formylphenyl)acetate|95%
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Quality Control of [ 142327-44-4 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 142327-44-4 ]

SDS Specification

Alternatived Products of [ 142327-44-4 ]

Product Details of [ 142327-44-4 ]

CAS No. :	142327-44-4	MDL No. :	MFCD15523582
Formula :	C₁₀H₁₀O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FFUBFLSGFOHPKF-UHFFFAOYSA-N
M.W :	178.18	Pubchem ID :	11819590
Synonyms :

Calculated chemistry of [ 142327-44-4 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.2
Num. rotatable bonds :	4
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	47.69
TPSA :	43.37 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) :	-6.56 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.86
Log Po/w (XLOGP3) :	1.17
Log Po/w (WLOGP) :	1.21
Log Po/w (MLOGP) :	1.32
Log Po/w (SILICOS-IT) :	2.21
Consensus Log Po/w :	1.56

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.76
Solubility :	3.1 mg/ml ; 0.0174 mol/l
Class :	Very soluble
Log S (Ali) :	-1.68
Solubility :	3.76 mg/ml ; 0.0211 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.83
Solubility :	0.267 mg/ml ; 0.0015 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.53

Safety of [ 142327-44-4 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338-P304+P340-P405	UN#:	N/A
Hazard Statements:	H302	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 142327-44-4 ]

* 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 [ 142327-44-4 ]
Downstream synthetic route of [ 142327-44-4 ]

[ 142327-44-4 ] Synthesis Path-Upstream 1~1

1
[ 142327-44-4 ]
[ 34956-29-1 ]

Reference： [1] Patent: WO2007/51062, 2007, A2, . Location in patent: Page/Page column 143-144

[ 142327-44-4 ] Synthesis Path-Downstream 1~88

1
[ 52798-00-2 ]
[ 142327-44-4 ]

Yield	Reaction Conditions	Operation in experiment
	With formic acid;aluminum nickel; In water; for 1.75h;Heating / reflux;	Step B (3-Formyl-phenyl)-acetic acid methyl ester. A mixture of (3-cyano-phenyl)-acetic acid methyl, ester prepared of Preparation 13, Step A (1.56 g, 8.91 mmol), aluminum-nickel alloy (1.63 g) and 75% formic acid (25, mL) was heated at reflux for 1.75 h. The mixture was cooled to room temperature and the solids were removed by filtration through Celite with the aid of boiling EtOH. Water was added, and the aqueous solution was washed with CH2Cl2 (3*). Aqueous saturated NaHCO3 was carefully added to the organic solution until the pH was about 8-9. The organic solution was washed with brine, dried over MgSO4, and concentrated. Purification by flash chromatography (5:1 hexanes:EtOAc) provided the title compound as a clear and colorless oil (870 mg). 1H NMR (400 MHz, CDCl3) delta 9.98 (s, 1H), 7.77 (m, 2H), 7.55-7.46 (m, 2H), 3.68 (s, 5H).
	With formic acid; sodium hydrogencarbonate; In ethanol; water;	Step B (3-Formyl-phenyl)-acetic acid methyl ester. A mixture of (3-cyano-phenyl)-acetic acid methyl ester (1.56 g, 8.91 mmol), aluminum-nickel alloy (1.63 g) and 75% formic acid (25 mL) was heated at reflux for 1.75 h. The mixture was cooled to room temperature and the solids were removed by filtration through Celite with the aid of boiling EtOH. Water was added and the aqueous solution was washed with CH2Cl2 (3*). Aqueous saturated NaHCO3 was carefully added to the organic solution until the pH was about 8-9. The organic solution was washed with brine, dried over MgSO4, and concentrated. Purification by flash chromatography (5:1 hexanes:EtOAc) provided the title compound as a clear and colorless oil (870 mg). 1H NMR (400 MHz, CDCl3) delta 9.98 (s, 1H), 7.77 (m, 2H), 7.55-7.46 (m, 2H), 3.68 (s, 5H).
	With formic acid; sodium hydrogencarbonate; In ethanol; water;	Step B (3-Formyl-phenyl)-acetic acid methyl ester A mixture of (3-cyano-phenyl)-acetic acid methyl ester (1.56 g, 8.91 mmol), aluminum-nickel alloy (1.63 g) and 75% formic acid (25 mL) was heated at reflux for 1.75 h. The mixture was cooled to room temperature and the solids were removed by filtration through Celite with the aid of boiling EtOH. Water was added and the aqueous solution was washed with CH2Cl2 (3*). Aqueous saturated NaHCO3 was carefully added to the organic solution until the pH was about 8-9. The organic solution was washed with brine, dried over MgSO4, and concentrated. Purification by flash chromatography (5:1 hexanes:EtOAc) provided the title compound as a clear and colorless oil (870 mg). 1H NMR (400 MHz, CDCl3) delta9.98 (s, 1H), 7.77 (m, 2H), 7.55-7.46 (m, 2H), 3.68 (s, 5H).

Reference： [1]Journal of the Chemical Society,1956,p. 404,410
[2]Journal of Organic Chemistry,1993,vol. 58,p. 4196 - 4197
[3]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492
[4]Patent: US2005/203086,2005,A1 .Location in patent: Page/Page column 46-47
[5]Patent: US6288120,2001,B1
[6]Patent: US6344485,2002,B1

2
[ 1192-06-9 ]
[ 142327-44-4 ]
[ 142327-16-0 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1402 - 1405

4
[ 142327-44-4 ]
[ 870194-97-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

5
[ 930294-72-7 ]
[ 142327-44-4 ]
Methyl [3-([3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl]amino}methyl)phenyl]acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		(iii) Methyl [3-([3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9- yl)propyl]amino}methyl)phenyl]acetate; s The product from step (ii) (3.Ig) and methyl (3-formylphenyl)acetate (1.6g) were dissolved in NMP (30ml) and stirred for 15min. Sodium triacetoxyborohydride (3.7g) was added and the mixture stirred at rt for 20 h. After addition of methanol (1 ml), the mixture was purified by SCX, which afforded the subtitle compound. Yield 3.1g.1H NMR delta (DMSO-d6) 7.27 - 7.21 (3H, m), 7.13 (IH, m), 6.46 (2H, brs), 4.12 (2H, t), 3.73 0 (2H, t), 3.70 (2H, s), 3.64 (2H, s), 3.61 (3H, s), 2.54 (2H, t), 1.82 (2H, m), 1.62 (2H, m), 1.37 (2H, m), 0.90 (3H, t).

Reference： [1]Patent: WO2008/4948,2008,A1 .Location in patent: Page/Page column 42

6
[ 621-37-4 ]
[ 142327-44-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

7
[ 42058-59-3 ]
[ 142327-44-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

8
[ 142327-44-4 ]
C₁₀H₁₀ClNO₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492
[2]Patent: WO2005/113519,2005,A1

9
[ 142327-44-4 ]
(3-{4-[2-(2,4-dichloro-phenoxy)-ethylcarbamoyl]-5-isopropyl-isoxazol-3-yl}-phenyl)-acetic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

10
[ 142327-44-4 ]
[ 927187-53-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

11
[ 142327-44-4 ]
[ 927187-47-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492
[2]Patent: WO2005/113519,2005,A1

12
[ 142327-44-4 ]
(3-{4-[2-(2,4-dichloro-phenoxy)-ethylcarbamoyl]-5-furan-2-yl-isoxazol-3-yl}-phenyl)-acetic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

13
[ 142327-44-4 ]
[ 927187-54-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

14
[ 142327-44-4 ]
LC₁₇₆₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492
[2]Patent: WO2005/113519,2005,A1

15
[ 142327-44-4 ]
[ 927187-56-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

16
[ 142327-44-4 ]
(3-{4-[2-(2,4-dichloro-phenoxy)-ethylcarbamoyl]-5-<i>o</i>-tolyl-isoxazol-3-yl}-phenyl)-acetic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

17
[ 142327-44-4 ]
(3-{5-(2-chloro-phenyl)-4-[2-(2,4-dichloro-phenoxy)-ethylcarbamoyl]-isoxazol-3-yl}-phenyl)-acetic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

18
[ 142327-44-4 ]
[ 927187-57-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

19
[ 147283-87-2 ]
[ 142327-44-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5488 - 5492

20
[ 621-36-3 ]
[ 142327-44-4 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1402 - 1405

21
[ 142327-44-4 ]
[ 155172-84-2 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1402 - 1405

22
[ 142327-44-4 ]
[ 1026038-84-5 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1402 - 1405

23
[ 142327-44-4 ]
[ 142327-17-1 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1402 - 1405

24
[ 142327-44-4 ]
7-chloro-4-hydroxy-3-[3-(3-thienylmethyl)phenyl]-2(1H)-quinolone [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1402 - 1405

25
[ 142327-44-4 ]
[ 1027842-70-1 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1402 - 1405

26
[ 118647-53-3 ]
[ 142327-44-4 ]

Reference： [1]Journal of Medicinal Chemistry,1994,vol. 37,p. 1402 - 1405

27
[ 150529-73-0 ]
[ 142327-44-4 ]

Reference： [1]Journal of Organic Chemistry,1993,vol. 58,p. 4196 - 4197
[2]Patent: WO2005/113519,2005,A1
[3]Patent: KR2019/137803,2019,A

28
[ 142327-44-4 ]
C₁₀H₁₁NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydroxylamine hydrochloride; N-ethyl-N,N-diisopropylamine; In 1,2-dimethoxyethane; at 20℃; for 2h;	Step D:; (3-Formylphenyl) -acetic acid methyl ester 48 (0.28 g, 1.6 mmol) is dissolved in dimethoxy-ethane (5 mL). Hydroxy-amine hydrochloride (0.11 g, 1.58 mmol) is added, followed by ethyl-diisopropylamine (0.3 mL, 1.7 mmol). The mixture is stirred at room temperature for 2 hours. The solvent is removed in vacuo and the residue is extracted three times with dichloromethane. The organic layers are combined, dried over MgS04, filtered, and concentrated to afford the oxime 49 as a white solid: ¹H-NMR (400MHz, CDC13) No. = 8.12 (s, 1H), 7.65-7.70 (m, 4H), 3.70 (s, 3H), 3.64 (s, 2H). MS calculated for CioH12N03 (M+H+) 194.1, found 104.1.

Reference： [1]Patent: WO2005/113519,2005,A1 .Location in patent: Page/Page column 49

29
[ 64-18-6 ]
[ 52798-00-2 ]
[ 142327-44-4 ]

Yield	Reaction Conditions	Operation in experiment
	With nickel; at 110℃; for 24h;	Step C:; A solution of (3-cyanophenyl) acid methyl ester 47 (0.86 g, 4.9 mmol) in 88% formic acid (6 mL) is combined with Raney nickel alloy (0.48 g) and heated to reflux for 24 hours at 110C. After cooling to room temperature, the alloy is removed by filtration over Celite. The filtrate is concentrated to ~10% of the original volume and diluted with EtOAc (50 mL) and washed three times with water (20 mL). The organic layer is dried (MgS04), filtered and concentrated to afford crude product, which is purified by silica gel chromatography using an EtOAc/hexane gradient to give (3-formylphenyl) -acetic acid methyl ester 48 as an oil: 'H-NMR (400MHz, CDC13) 8 = 9.97 (s, 1H), 7.40-7.52 (m, 4H), 3.68 (s, 3H), 3.67 (s, 2H). MS calculated for C10H11O3 (M+H+) 179.1, found 179.1.

Reference： [1]Patent: WO2005/113519,2005,A1 .Location in patent: Page/Page column 49

30
[ 57802-79-6 ]
[ 142327-44-4 ]
[ 210115-56-3 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium cyanoborohydride; In 1,4-dioxane; methanol; at 20.0℃;	(3-((<strong>[57802-79-6]4-Butyl-benzylamin</strong>o)-methyl)-phenyl)-acetic acid methyl ester. A solution of <strong>[57802-79-6]4-butyl-benzylamine</strong> (from Preparation 15, 0.918 g, 6 mmol) in MeOH was added to 4N HCl in dioxane (0.75 mL, 3 mmol) followed by addition of (3-formyl-phenyl)-acetic acid methyl ester (from Preparation 13, 0.534 g, 3.0 mmol). NaCNBH3 (0.194 mL, 3 mmol) was added and the reaction was stirred at room temperature overnight. The mixture was diluted with EtOAc and 2N NaOH was added. The organic solution was dried over MgSO4, filtered, and concentrated in vacuo. The product was purified via flash chromatography (50% hexanes, 50% EtOAc, 0.1% Et3N) to afford the title compound of Step A. 1H NMR (400 MHz, CDCl3) delta 7.08-7.38 (m, 8H), 3.75 (s, 2H), 3.73 (s, 2H), 3.70 (s, 3H), 3.62 (s, 2H), 2.61 (t, 2H), 1.58 (m, 2H), 1.37 (m, 2H), 0.92 (t, 3H); MS 326 (M+1).
	With hydrogenchloride; NaCNBH3; In 1,4-dioxane; methanol;	Step A: Reductive Amination (3-((<strong>[57802-79-6]4-Butyl-benzylamin</strong>o)-methyl)-phenyl)-acetic acid methyl ester. A solution of <strong>[57802-79-6]4-butyl-benzylamine</strong> (from Preparation 15, 0.918 g, 6 mmol) in MeOH was added to 4N HCl in dioxane (0.75 mL, 3 mmol) followed by addition of (3-formyl-phenyl)-acetic acid methyl ester (from Preparation 13, 0.534 g, 3.0 mmol). NaCNBH3 (0.194 mL, 3 mmol) was added and the reaction was stirred at room temperature overnight. The mixture was diluted with EtOAc and 2N NaOH was added. The organic solution was dried over MgSO4, filtered, and concentrated in vacuo. The product was purified via flash chromatography (50% hexanes, 50% EtOAc, 0.1% Et3N) to afford the title compound of Step A. 1H NMR (400 MHz, CDCl3) delta 7.08-7.38 (m, 8H), 3.75 (s, 2H), 3.73 (s, 2H), 3.70 (s, 3H), 3.62 (s, 2H), 2.61 (t, 2H), 1.58 (m, 2H), 1.37 (m, 2H), 0.92 (t, 3H); MS 326 (M+1).

Reference： [1]Patent: US2005/203086,2005,A1 .Location in patent: Page/Page column 43
[2]Patent: US6498172,2002,B1

Yield	Reaction Conditions	Operation in experiment
		Aqueous saturated NaHCO3 was carefully added to the organic solution until the pH was about 8-9. The organic solution was washed with brine, dried over MgSO4, and concentrated. Purification by flash chromatography (5:1 hexanes:EtOAc) provided the title compound as a clear and colorless oil (870 mg). 1H NMR (400 MHz, CDCl3) delta 9.98 (s, 1H), 7.77 (m, 2H), 7.55-7.46 (m, 2H), 3.68 (s, 5H).
		The ester (2.5 g) was added to sodium hydrogencarbonate (5 g) in dimethylsulphoxide (35 ml) at 120 C. After 20 min the mixture was cooled in an ice bath, diluted with water and extracted with ether (*3). The ethereal extracts were washed with water and brine, dried, evaporated in vacuo, and purified by flash chromatography eluding with hexane:ethyl acetate (4:1 v/v) to give methyl 3-formylphenylacetate (2.02 g) as an oil; deltaH (360 MHz, CDCl3) 3.71 (5H, s, CH2 and Me), 7.25-7.4 (2H, m, ArH), 7.8-7.85 (2H, m, ArH), 10.0 (1H, s, CHO); m/z (EI+) 178 (M+).

32
9-(2-aminoethyl)-butoxy-8-methoxy-9H-purin-6-amine [ No CAS ]
[ 142327-44-4 ]
[ 866268-35-1 ]

Yield	Reaction Conditions	Operation in experiment
		(viii) Methyl [3-([2-(6-amino2-butoxy-8-methoxy-9H-purin-9-yl)ethyl]amino}methyl)phenyl]acetate The compound obtained in the step (vii) (200mg) and methyl (3-formylphenyl)acetate (133mg) were dissolved in methanol (5ml) and the mixture was stirred at room temperature for 4 hours. Sodium borohydride (32mg) was added and the mixture was stirred at room temperature overnight. To the reaction solution were added dichloromethane (100ml) and water (100ml) and the organic layer was separated, washed with water and saturated brine and dried. To the obtained solution was added polymer supported aldehyde resin (300mg) and the mixture was agitated at room temperature overnight. The resin was removed by filtration and the filtrate was concentrated under reduced pressure to give the titled compound 200mg. The product was used in the next reaction without further purification. MS APCI+ve 444 (M+H).

Reference： [1]Patent: EP1728793,2006,A1 .Location in patent: Page/Page column 56

33
[ 930294-72-7 ]
[ 142327-44-4 ]
methyl (3-[[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl](1-methylpiperidin-4-yl)amino]methyl}phenyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The product of example 1 step (vii) (430mg), iV-methylpiperidone (191mg), sodium triacetoxyborohydride (l.lg) and acetic acid (0.5ml) were stirred together in NMP (10ml) at 50 0C for 2 h. The mixture was cooled to rt and treated with SCX. After concentration in vacuo, the residue was dissolved in NMP (10ml) and methyl (3-formylphenyl)acetate 0 (222mg), sodium triacetoxyborohydride l.lg and a few drops of acetic acid added. The mixture was stirred at 45 0C for 24 h. The mixture was cooled to rt, treated with SCX and purified by RPHPLC, to afford the title compound, yield 370mg.1H NMR delta (CDCl3) 7.22 - 7.05 (4H, m), 5.39 (2H, s), 4.25 (2H, t), 3.81 (2H, t), 3.71 (3H, 5 s), 3.64 - 3.61 (2H, m), 3.59 - 3.56 (2H, m), 2.91 - 2.83 (2H, m), 2.59 - 2.43 (3H, m), 2.23 (3H, s), 1.98 - 1.19 (12H, m), 1.00 - 0.92 (3H, m). MS: APCI (+ve): 540 (M+H)

Reference： [1]Patent: WO2007/34173,2007,A1 .Location in patent: Page/Page column 35

34
[ 930294-74-9 ]
[ 142327-44-4 ]
[ 930294-52-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; acetic acid; In 1-methyl-pyrrolidin-2-one; at 45℃; for 24h;	A mixture of the product from step (iii) (0.34g), methyl (3-formylphenyl)acetate (150mg), sodium triacetoxyborohydride (652mg) and acetic acid (0.5ml) in NMP (10ml) were stirred together at 45 0C for 24 h. The mixture was cooled to rt, treated with SCX and purified by RPHPLC, to afford the title compound, yield 240mg.1H NMR delta (DMSO-d6) 9.80 (IH, s), 7.38 - 7.16 (8H, m), 7.13 - 7.07 (IH, m), 6.38 (2H, s), 4.13 (2H, t), 3.69 - 3.61 (4H, m), 3.59 (3H, s), 3.57 (2H, s), 3.42 (3H, s), 3.31 (2H, s), 2.88 - 2.78 (2H, m), 1.90 - 1.21 (12H, m), 0.91 (3H, t). MS: APCI (+ve): 616 (M+H)

Reference： [1]Patent: WO2007/34173,2007,A1 .Location in patent: Page/Page column 38

35
[ 930294-75-0 ]
[ 142327-44-4 ]
methyl (3-[[4-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)butyl](1-methylpiperidin-4-yl)amino]methyl}phenyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The product of step (ii) (560mg), methyl (3-formylphenyl)acetate (286mg) and sodium triacetoxyborohydride (922mg) were stirred together in NMP (20ml) at 5O0C for 24 h. The mixture was cooled to rt, treated with SCX and purified by RPHPLC. Methanol (5ml) and 4M-HC1 in dioxane (ImI) were added and stirred at rt overnight. The mixture was concentrated in vacuo, to afford the title compound, yield 130mg. EPO <DP n="42"/>1H NMR delta (DMSOd6) 9.84 (IH, s), 7.22 - 7.10 (3H, m), 7.08 - 7.03 (IH, m), 6.38 (2H, s), 4.12 (2H3 1), 3.66 - 3.54 (5H, m), 3.51 (2H, s), 3.32 (3H, s), 2.73 (2H, d), 2.46 - 2.36 (2H, m), 2.35 - 2.25 (2H, m), 2.08 (3H, s), 1.72 - 1.17 (12H, m), 0.90 (3H, t). MS: APCI (+ve): 554 (M+H)

Reference： [1]Patent: WO2007/34173,2007,A1 .Location in patent: Page/Page column 39-40

36
[ 142327-44-4 ]
[ 79099-07-3 ]
[ 930294-44-3 ]

Yield	Reaction Conditions	Operation in experiment
		The product of step (vii) (0.5Og) and 4-oxo-piperidine-l-carboxylic acid tert-bntyl ester (0.39g) were stirred together with 3 drops of glacial acetic acid in NMP (20ml) at rt for 5 min. Sodium triacetoxyborohydride (1.13g) was added, and the solution stirred at 4O0C overnight. Methyl (3-formylphenyl)acetate (0.38g) was added along with a further Ig of sodium triacetoxyborohydride and the mixture stirred overnight. A further 0.2g of methyl (3-formylphenyl)acetate was added and the mixture left at 4O0C for 24 h. The mixture was Q purified by SCX and the product dissolved in a mixture of DCM/TFA (3/1 , 40ml). After stirring at rt for 24 h, the mixture was concentrated in vacuo and the residue purified by RPetaPLC, yield 0.5Og.1H NMR delta (DMSOd6) 7.26 - 7.17 (4eta, m), 7.12 - 7.03 (2H, m), 6.38 (2H, s), 4.11 (3H, t), s 3.66 - 3.60 (4H, m), 3.58 (3H, s), 3.55 (IH, s), 2.96 - 2.90 (2H, m), 2.50 - 2.42 (2H, m), 2.36 - 2.28 (2H, m), 1.78 - 1.70 (2H, m), 1.65 - 1.56 (4H, m), 1.40 - 1.34 (2H, m), 1.33 - 1.26 (2H, m), 0.90 (3H, t). MS: APCI (+ve): 526 (M+H)

Reference： [1]Patent: WO2007/34173,2007,A1 .Location in patent: Page/Page column 33

37
[ 142327-44-4 ]
[ 34956-29-1 ]

Yield	Reaction Conditions	Operation in experiment
		Synthesis of (3-Formyl-phenyl)-acetic acid (24d): Lithium hydroxide (89.3 mg, 3.72 mmol) was added to a solution of <strong>[142327-44-4](3-Formyl-phenyl)-acetic acid methyl ester</strong> (221 mg, 1.24 mmol) in 50 mL water/methanol (5/1) and stirred at room temperature overnight. After the methanol was removed in vacuo the reaction was acidified to pHl with IM HCl. The aqueous layer was extracted with dichloromethane, and chloroform. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 181.9 mg of (3-Formyl-phenyl)-acetic acid.

Reference： [1]Patent: WO2007/51062,2007,A2 .Location in patent: Page/Page column 143-144

38
6-amino-2-butoxy-9-(3-[2-(dimethylamino)ethyl]amino}propyl)-7,9-dihydro-8H-purin-8-one [ No CAS ]
[ 142327-44-4 ]
[ 929551-96-2 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; In 1-methyl-pyrrolidin-2-one; 1,2-dichloro-ethane; at 20℃; for 4h;	The product from step (i) (500mg) was dissolved in a mixture of 1,2-dichloroethane (12ml) and l-methyl-2-pyrrolidinone (3ml). <strong>[142327-44-4](3-Formyl-phenyl)-acetic acid methyl ester</strong> (300mg) o and sodium triacetoxyborohydride (425mg) were added and the mixture stirred at ambient temperature for 4 hours. After removing the solvent, the residue was partitioned between dichloromethane (100ml) and saturated aqueous sodium hydrogen carbonate (100ml), the organic layer dried and concentrated in vacuo. The residue was purified by RPHPLC to afford the title compound. Yield 260mg. 51H ?MR ? (DMSO-d6) 9.82 (IH, s), 7.24 - 7.16 (3H, m), 7.10 (IH, d), 6.38 (2H, s), 4.12 (2H, t), 3.68 (2H, t), 3.64 (2H, s), 3.59 (3H, s), 3.52 (2H, s), 2.45 - 2.41 (4H, m), 2.27 - 2.23 (2H, m), 2.04 (6H, s), 1.85 - 1.80 (2H, m), 1.65 - 1.58 (2H3 m), 1.39 - 1.33 (2H, m), 0.90 (3H, t). o MS: APCI (+ve): 514

Reference： [1]Patent: WO2007/31726,2007,A1 .Location in patent: Page/Page column 32

39
[ 2038-57-5 ]
[ 142327-44-4 ]
C₁₉H₂₃NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		a) (3-[terf-Butoxycarbonyl-(3-phenyl-propyI)-amino]-methyl}-phenyl)-acetic acid methyl ester; Sodium triacetoxyborohydride (2.Og) was added to a solution of 3-phenylpropyl-l-amine (0.6g) and <strong>[142327-44-4](3-formyl-phenyl)-acetic acid methyl ester</strong> (0.52g) in dichloromethane (1OmL). After 4 hours, the reaction mixture was poured on to saturated aqueous sodium bicarbonate solution and extracted with dichloromethane (2x50mL). The combined organics were dried (sodium sulfate), filtered and di-tert-butyl dicarbonate (1.Og) added to the filtrate. After 18 hours, the reaction mixture was evaporated and the residue purified on silica, eluting with methanol (1%) in dichloromethane, to give the subtitle compound as an oil (0.93g).1H NMR (400 MHz, CDCl3) delta 7.30 - 7.23 (m, 2H), 7.20 - 7.10 (m, 7H), 4.42 (d, 2H), 3.69 (s, 3H), 3.60 (s, 2H), 3.15 (q, 2H), 2.56 (t, 2H), 1.85 - 1.77 (m, 2H), 1.44 (s, 9H).

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 91

40
[ 110-89-4 ]
[ 142327-44-4 ]
C₁₅H₂₁NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		a) l-Boranyl-l-[3-(2-hydroxy-ethyl)-benzyl]-piperidinium; <strong>[142327-44-4](3-Formyl-phenyl)-acetic acid methyl ester</strong> (0.64g), acetic acid (0.18 mL) and piperidine (0.29mL) were combined in dichloromethane (1OmL). After 1 hour, sodium triacetoxyborohydride (0.95 g) was added and the reaction stirred overnight. After 24 hours, the solvent was evaporated. The resultant residue was loaded onto a conditioned SCX cartridge (1Og Varian) and washed with methanol (5OmL), then eluted with methanolic ammonia solution (5OmL). The elution fraction was evaporated and the residue was dissolved in ethanol (1OmL). Calcium chloride anhydrous (0.67 g) was added followed by sodium borohydride (0.45 g) and the resulting mixture stirred overnight. Aqueous potassium carbonate solution (2M, 5OmL) was added and the ethanol evaporated. The aqueous was extracted with ethyl acetate (3x50mL) and the combined organics washed with water (5OmL), brine (5OmL), dried (sodium sulfate) and evaporated. The residue was redissolved in tetrahydrofuran (1OmL) and cooled to 0C, under nitrogen. Bbrane-methyl sulfide complex (2M solution in tetrahydrofuran, 2.25mL) was added and the resulting mixture stirred for 5 minutes. The tetrahydrofuran was evaporated and the residue purified on silica, eluting with diethyl ether / iso-hexane [1:1 to 1:0] to give subtitle product, as an oil (133mg).1H NMR (400 MHz, CDCl3) delta 7.34 - 7.28 (m, 2H)5 7.27 - 7.23 (m, 2H), 3.99 (s, 2H), 3.88 (q, 2H), 2.96 - 2.86 (m, 4H)32.69 - 2.60 (m, 2H), 2.22 - 2.10 (m, 2H), 1.71 - 1.56 (m, 3H), 1.35 - 1.26 (m, IH).

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 92

41
[ 110-89-4 ]
[ 142327-44-4 ]
[ 878139-92-5 ]

Yield	Reaction Conditions	Operation in experiment
		a) 2-(4-Piperidin-l-ylmethylphenyl)ethanol; A solution of piperidine (204mg) and (4-formylphenyl)acetic acid methyl ester (Example 16, step a, 356mg) in dichloromethane (1OmL) was stirred for 1 hour, treated with sodium triacetoxyborohydride (636mg) and stirred overnight. The resultant mixture was loaded onto a conditioned SCX cartridge (1Og5 Varian) and washed with methanol (5OmL), then eluted with methanolic ammonia solution (5OmL). The elution fraction was evaporated and the residue was dissolved in ethanol (2OmL), treated with anhydrous calcium chloride (444mg), followed by sodium borohydride (303mg) and stirred overnight. The mixture <n="124"/>was quenched with aqueous potassium carbonate solution (2M5 2OmL) and concentrated to remove most of the ethanol. The residue was extracted with ethyl acetate and the washed and dried (sodium sulfate) extract was evaporated. The residue was purified on silica, eluting with 5% triethyamine in diethyl ether to give the subtitle product, as a colourless oil (287mg).1H NMR (300MHz, CDCl3) delta 7.26 (d, 2H), 7.17 (d, 2H), 3.86 (t, 2H)5 3.44 (s, 2H), 2.86 (t, 2H), 2.38 - 2.34 (m, 4H), 1.60 - 1.41 (m, 6H), OH not seen.

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 122

42
[ 110-91-8 ]
[ 142327-44-4 ]
C₁₄H₁₉NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; In methanol; for 24h;	a) Trihydrido(2-{3-[2-(morpholin-4-yl-kappaiV)ethyl]phenyl}ethanol)boron; <strong>[142327-44-4](3-Formyl-phenyl)-acetic acid methyl ester</strong> (Example 1, step a, 540mg), acetic acid (0.18mL) and morpholine (0.29mL) were combined in methanol (1OmL), sodium triacetoxyborohydride (950mg) was then added. After 24 hours, the solvent was evaporated. The resultant residue was loaded onto a conditioned SCX cartridge (50g, Varian) and washed with methanol (25OmL), then eluted with methanolic ammonia solution (2M, 15OmL). The elution fraction was evaporated and the residue was dissolved in ethanol (1OmL). Calcium chloride anhydrous (1.Og) was added followed by sodium borohydride (680mg) and the resulting mixture stirred overnight. An aqueous potassium carbonate solution (2M, 5OmL) was added and the mixture filtered. The filtrate was extracted with ethyl actetate (3x5 OmL) and the combined organics washed with water (5OmL), brine (5OmL), dried (sodium sulfate) and evaporated. The residue was redissolved in tetrahydrofuran (1OmL) and cooled to O0C, under nitrogen. Borane-methyl sulfide <n="150"/>complex (2M solution in tetrahydrofuran, 2.25mL) was added and the resulting mixture stirred for 5 minutes. The tetrahydrofuran was evaporated and the residue purified on silica, eluting with ethyl acetate : zso-hexane [0:1 to 1:1] to give subtitle product, as an oil 350mg. 1H NMR (400 MHz, CDCl3) delta 7.38 - 7.10 (m, 4H), 4.40 - 4.25 (m, 2H), 4.10 - 4.01 (m, 2H)5 3.98 - 3.82 (m, 2H), 3.75 - 3.57 (m, 2H), 2.94 - 2.68 (m, 4H), 2.50 - 2.38 (m, 2H). + 4 exchangable protons not seen.

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 148-149

43
[ 123-75-1 ]
[ 142327-44-4 ]
C₁₃H₁₉NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; acetic acid; In methanol; for 24h;	a) Trihydrido(2-{3-[2-(pyrrolidin-l-yl-kappalambda0ethyl]phenyl}ethanol)boron; <n="122"/><strong>[142327-44-4](3-Formyl-phenyl)-acetic acid methyl ester</strong> (Example I5 step a, 540mg), acetic acid (0.18mL) and pyrrolidine (230mg) were combined in methanol (1OmL), sodium triacetoxyborohydride (950mg) was then added. After 24 hours, the solvent was evaporated. The resultant residue was loaded onto a conditioned SCX cartridge (5Og, Varian) and washed with methanol (25OmL), then eluted with methanolic ammonia solution (2M, 15OmL). The elution fraction was evaporated and the residue was dissolved in ethanol (1OmL). Calcium chloride anhydrous (1.Og) was added followed by sodium borohydride (680mg) and the resulting mixture stirred overnight. An aqueous potassium carbonate solution (2M, 5OmL) was added and the mixture filtered. The filtrate was extracted with ethyl actetate (3x5 OmL) and the combined organics washed with water (5OmL), brine (5OmL), dried over sodium sulfate and evaporated. The residue was redissolved in tetrahydrofuran (1OmL) and cooled to 0C, under nitrogen. Borane-methyl sulfide complex (2M solution in tetrahydrofuran, 4.5mL) was added and the resulting mixture stirred for 5 minutes. The tetrahydrofuran was evaporated and the residue purified on silica, eluting with diethyl ether : w°-hexane [0:1 to 1:1] to give subtitle product, as an oil 420mg.H NMR (300 MHz, CDCl3) delta 7.36 - 7.20 (m, 4H), 4.02 (s, 2H), 3.88 (q, 2H), 3.14 - 3.03 (m, 2H), 2.94 - 2.79 (m, 4H), 2.23 - 2.11 (m, 2H), 1.84 - 1.72 (m, 2H). + 4 exchangable protons not seen.

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 120-121

44
[ 111-49-9 ]
[ 142327-44-4 ]
C₁₆H₂₃NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; In methanol; for 24h;	a) (2-{3-[2-(azepan-l-yl-idV)ethyI]phenyl}ethanol)(trihydrido)boron; <strong>[142327-44-4](3-Formyl-phenyl)-acetic acid methyl ester</strong> (Example 1, step 1, 0.54g), acetic acid (0.18mL) and azepane (ImL) were combined in methanol (1OmL), sodium triacetoxyborohydride (950mg) was then added. After 24 hours, the solvent was <n="148"/>evaporated. The resultant residue was loaded onto a conditioned SCX cartridge (5Og, Varian) and washed with methanol (25OmL), then eluted with methanolic ammonia solution (2M, 15OmL). The elution fraction was evaporated and the residue was dissolved in ethanol (1OmL). Calcium chloride anhydrous (LOg) was added followed by sodium borohydride (680mg) and the resulting mixture stirred overnight. An aqueous potassium carbonate solution (2M, 5OmL) was added and the mixture filtered. The filtrate was extracted with ethyl actetate (3x50mL) and the combined organics washed with water (5OmL), brine (5OmL), dried (sodium sulfate) and evaporated. The residue was redissolved in tetrahydrofuran (1OmL) and cooled to 0C, under nitrogen. Borane-methyl sulfide complex (2M solution in tetrahydrofuran, 4.5mL) was added and the resulting mixture stirred for 5min. The tetrahydrofuran was evaporated and the residue purified on silica, eluting with diethyl ether : zso-hexane [0:1 to 1:1] to give subtitle product, as an oil 550mg. 1HNMR (400 MHz, CDCl3) delta 7.35 (s, IH), 7.32 - 7.23 (m, 3H)5 3.91 (s, 2H), 3.87 (t, 2H)5 3.07 (dd, 2H), 2.96 (dd, 2H), 2.89 (t, 2H), 1.93 - 1.80 (m, 2H), 1.63 - 1.42 (m, 6H). + 1 exchangable proton not seen.

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 146-147

45
[ 142327-44-4 ]
[ 89-99-6 ]
C₁₇H₁₈FNO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		a) (2-Fluoro-benzyl)-[3-(2-hydroxy-ethyl)-benzyI]-carbamic acid tert-butyl ester; A mixture of (3-formyl-phenyl)-acetic acid ethyl ester (400mg), (2-fluorobenzyl)amine (410mg) and acetic acid (130mg) in methanol (5mL) was stirred at room temperature. After Ih, sodium triacetoxyborohydride (700mg) was added. After 5 hours, the reaction mixture was neutralised with aqueous ammonia (0.880) and the solution evaporated to dryness. The residue was diluted with toluene and the mixture evaporated. The resulting gum was dissolved in methanol and applied to a SCX cartridge (7Og, varian). The cartridge was eluted with methanol (25OmL) and then 20% ammonia in methanol to collect the reductive amination product. The solution was evaporated and the gum dissolved in ethanol. Anhydrous calcium chloride (730mg) was added followed by careful portionwise addition of sodium borohydride (500mg). After 16 hours, the reaction mixture was quenched with 2M aqueous potassium carbonate (2OmL). The solid was removed by filtration, the filtrate evaporated and the residue partitioned between ethyl acetate and brine. The organic solution was dried over magnesium sulphate, filtered and evaporated. Purification was by silica gel chromatography eluting with ethyl acetate:dichloromethane 1:3, then ethyl acetate -.dichloromethane 1:3 containing 5% triethylamine, to give 2-{3-[(2- fluoro-benzylamino)-methyl]-phenyl}-ethanol (320mg). Without further purification the 2- {3-[(2-fluoro-benzylamino)-methyl]-phenyl} -ethanol was dissolved in dichloromethane <n="137"/>(5mL) and di-tert-butyl dicarbonate (300mg) added. After 3 hours, the solution was applied to a silica gel column eluting with ethyl acetate :dichloromethane 1:9 to give the subtitle compound (300mg).1H NMR (400 MHz, CDCl3) delta 7.30-6.95 (m, 8H), 4.50-4.30 (m, 4H), 3.81 (q, 2H)3 2.82 (t, 2H), 1.46 (9H, s).

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 135-136

46
[ 16728-59-9 ]
[ 142327-44-4 ]
C₁₆H₂₅NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		a) [3-(2-Hydroxy-ethyl)-benzyl]-(3-propoxy-propyl)-carbamic acid tert-butyl ester; A mixture (3-formyl-phenyl)-acetic acid ethyl ester (530mg), (3-propoxypropyl)amine (1.5g) and acetic acid (0.17mL) in methanol (15mL) was stirred at room temperature for 15 minutes. Sodium triacetoxyborohydride (950mg) was added. After 5 hours, the reaction mixture was neutralised with aqueous ammonia (0.880) and the solution evaporated to dryness. The residue was diluted with toluene and the mixture evaporated. The resulting gum was dissolved in methanol and applied to a SCX cartridge (7Og, varian). The cartridge was eluted with methanol (25OmL) and then 20% ammonia in methanol to collect the reductive amination product. Toluene was added and the solution was evaporated. The <n="140"/>crude product was dissolved in dichloromethane (2OmL) and di-tert-butyl dicarbonate (1.8g) added. After 16 hours, the solution was evaporated, the residue dissolved in ethanol (3OmL), anhydrous calcium chloride (1.Og) added, followed by portionwise addition of sodium borohydride (700mg). After 16 hours, the reaction mixture was quenched with 2M aqueous potassium carbonate (2OmL), filtered and evaporated. The residue was partitioned between ethyl acetate and brine. The organic solution was dried over sodium sulphate, filtered and evaporated. Purification was by silica gel chromatography eluting with ethyl acetate: dichloromethane 1:4 to give the subtitle compound (300mg). 1U NMR (400 MHz, CDCl3) delta 7.35-7.30 (m, IH), 7.20-7.04 (m, 3H), 4.50-4.40 (m, 2H), 3.84 (q, 2H), 3.45-3.35 (m, 2H), 3.32 (t, 2H), 3.30-3.20 (m, 2H), 2.85 (t, 2H), 1.90-1.70 (m, 2H), 1.65-1.50 (m, 2H), 1.50-1.40 (br s, 9H), 0.90 (t, 3H).

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 138-139

47
[ 932-30-9 ]
[ 142327-44-4 ]
[ 950503-81-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 20℃; for 18h;	a) {3-[(2-Hydroxy-benzylamino)-methyl]-phenyl}-acetic acid methyl ester; A mixture of 2-hydroxybenzylamine (407mg) and (3-formylphenyl)acetic acid methyl ester (594mg) in dichloromethane (1OmL) and l-methyl-2-rhoyrrolidone (1OmL) was treated with acetic acid (333mg) followed by sodium triacetoxyborohydride (1.4Ig) and the whole stirred at room temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate, the organic layer was washed twice with saturated aqueous brine before being separated, dried and evaporated under reduced pressure to yield the sub-titled compound (0.8Ig). <n="134"/>m/z 286 (M+H)+ (APCI)

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 132-133

48
[ 771-99-3 ]
[ 142327-44-4 ]
C₂₁H₂₅NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		l-Boranyl-l-[3-(2-hydroxy-ethyl)-benzyl]-4-phenyl-piperidinium; <strong>[142327-44-4](3-Formyl-phenyl)-acetic acid methyl ester</strong> (0.64g), acetic acid (0.18mL) and 4-phenyl- piperidine (0.48mL) were combined in dichloromethane (1OmL). After 1 hour, sodium triacetoxyborohydride (0.95 g) was added and the reaction stirred overnight. After 24 hours, the solvent was evaporated. The resultant residue was loaded onto a conditioned SCX cartridge (1Og, Varian) and washed with methanol (5OmL), then eluted with methanolic ammonia solution (2M, 5OmL). The elution fraction was evaporated and the residue was dissolved in ethanol (1OmL). Calcium chloride anhydrous (0.67 g) was added followed by sodium borohydride (0.45 g) and the resulting mixture stirred overnight. An aqueous potassium carbonate solution (2M, 5OmL) was added and the ethanol evaporated. The aqueous was extracted with ethyl actetate (3x5 OmL) and the combined organics washed with water (5OmL), brine (5OmL), dried (sodium sulfate) and evaporated. The residue was redissolved in tetrahydrofuran (1OmL) and cooled to 0C, under nitrogen. Borane-methyl sulfide complex (2M solution in tetrahydrofuran, 2.25mL) was added and the resulting mixture stirred for 5min. The tetrahydrofuran was evaporated and the residue purified on silica, eluting with diethyl ether : wo-hexane [1:1 to 1:0] to give subtitle product, as an oil 193mg. 1K NMR (300 MHz, CDCl3) delta 7.39 - 7.14 (m, 9H), 4.09 (s, 2H), 3.95 - 3.87 (m, 2H), 3.05 (d, 2H), 2.92 (t, 2H), 2.75 - 2.58 (m, 4H), 2.45 - 2.33 (m, IH), 1.72 - 1.60 (m, 2H)

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 94

49
[ 142327-44-4 ]
[ 589-08-2 ]
C₁₉H₂₃NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		a) iV-Boranyl-2-{3-[(Methyl-phenethyl-ammonium)-methyl]-phenyl}-ethanol; 5 <strong>[142327-44-4](3-Formyl-phenyl)-acetic acid methyl ester</strong> (0.64g), acetic acid (0.18 mL) and methyl- phenethyl-amine (0.44 mL were combined in dichloromethane (10 mL). After 1 hour, sodium triacetoxyborohydride (0.95 g) was added and the reaction stirred overnight. After 24 hours, the solvent was evaporated. The resultant residue was loaded onto a conditioned <n="97"/>SCX cartridge (1Og Varian) and washed with methanol (5OmL), then eluted with methanolic ammonia solution (2M, 5OmL). The elution fraction was evaporated and the residue was dissolved in ethanol (1OmL). Calcium chloride anhydrous (0.67 g) was then added followed by sodium borohydride (0.45 g) and the resulting mixture stirred overnight. An aqueous potassium carbonate solution (2M, 5OmL) was added and the ethanol evaporated. The aqueous was extracted with ethyl actetate (3x50mL) and the combined organics washed with water (5OmL), brine (5OmL), dried over sodium sulfate, filtered, and evaporated. The residue was redissolved in tetrahydrofuran (1OmL) and cooled to 00C under N2. Borane-methyl sulfide complex (2M soln in THF3 2.25 mL) was added and the resulting mixture stirred for 5min. The tetrahydrofuran was evaporated and the residue purified on silica, eluting with diethyl ether : wo-hexane [1:1 to 1:0], to give subtitle product, as an oil (446mg).1HNMR (300 MHz, CDCl3) delta 7.38 - 7.16 (m, 9H), 4.12 (d, IH), 3.99 (d, IH), 3.85 (t, 2H), 3.28 - 3.11 (m, 2H), 2.91 - 2.73 (m, 4H), 2.54 (s, 3H).

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 95-96

50
[ 142327-44-4 ]
[ 57260-71-6 ]
C₁₉H₂₈N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; acetic acid; In methanol; for 24h;	a)Trihydrido (4-idV-[3-(2-Hydroxy-ethyl)-benzyl]-piperazine-l-carboxylic acid tert- butyl ester) boron; <strong>[142327-44-4](3-Formyl-phenyl)-acetic acid methyl ester</strong> (Example 1, step 1, 0.54g), acetic acid (0.18mL) and Boc-piperazine (0.62g) were combined in methanol (1OmL), sodium triacetoxyborohydride (950mg) was then added. After 24 hours, the solvent was evaporated. The resultant residue was loaded onto a conditioned SCX cartridge (5Og, Varian) and washed with methanol (25OmL), then eluted with methanolic ammonia solution (2M5 15OmL). The elution fraction was evaporated and the residue was dissolved in ethanol (1OmL). Calcium chloride anhydrous (1.Og) was added followed by sodium borohydride (680mg) and the resulting mixture stirred overnight. An aqueous potassium carbonate solution (2M5 5OmL) was added and the mixture filtered. The filtrate was extracted with ethyl actetate (3x50mL) and the combined organics washed with water (5OmL)5 brine (5OmL)5 dried (sodium sulfate) and evaporated. The residue was redissolved in tetrahydrofuran (1OmL) and cooled to 00C5 under nitrogen. Borane-methyl sulfide complex (2M solution in tetrahydrofuran, 4.5mL) was added and the resulting mixture stirred for 5min. The tetrahydrofuran was evaporated and the residue purified on silica, eluting with diethyl ether : zso-hexane [0:1 to 1:1] to give subtitle product, as an oil 55Omg. <n="163"/>1H NMR (299.946 MHz, CDCL3) delta 7.37 - 7.16 (m, 4H), 4.05 (s, 2H), 3.93 - 3.66 (m, 6H), 2.94 - 2.78 (m, 4H), 2.75 - 2.59 (m, 2H), 1.42 (s, 9H) +1 exchangable proton not seen.

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 161-162

51
[ 142327-44-4 ]
[ 5136-97-0 ]
C₁₈H₂₁NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		a) [3-({te^-Butoxycarbonyl-[2-(2-hydroxy-phenyl)-ethyI]-amino}-methyl)-phenyl]- acetic acid methyl ester; A mixture of 2-hydroxyphenethylamine hydrobromide salt (480mg) and (3- formylphenyl)acetic acid methyl ester prepared as described in Example 1 (step a, 370mg) in dichloromethane (1OmL) and l-methyl-2-pyrrolidone (2mL) was stirred for 30 minutes and then treated with sodium triacetoxyborohydride (1.02g) The mixture was stirred for 18 hours and at the end of this time partitioned between ethyl acetate and saturated aqueous sodium bicarbonate, the organic layer was separated, dried and the solvent removed under reduced pressure. The residue was dissolved in dichloromethane (2OmL) and treated with di-t°t-butyl-dicarbonate (480mg). The solution was stirred for 5 hours, at the end of this time the solvent was removed under reduced pressure. The residue was purified on silica eluting with 20% ethyl acetate in isohexane to yield the sub-titled compound (560mg). m/z 398 (M-H)- (APCI)

Reference： [1]Patent: WO2007/106016,2007,A1 .Location in patent: Page/Page column 130

52
[ 930777-69-8 ]
[ 142327-44-4 ]
[ 930777-71-2 ]

Yield	Reaction Conditions	Operation in experiment
67%		Example 5; 7,8-Dihydro-9-[1-(3-{N-[3-(methoxylcarbonylmethyl)benzyl]-N-methylamino}propyl)piperidin-4-ylmethyl]-2-(2-methoxyethoxy)-8-oxoadenine; [Show Image] Step (i); 8-Methoxy-9-[1-(3-{N-[3-(methoxylcarbonylmethyl)benzyl]-N-methylamino}propyl)piperidin-4-ylmethyl]-2-(2-rnethoxyethoxy)adenine; [Show Image] To the compound 423g (0.836mmol) obtained by example 4 step (i) was added trifluoroacetic acid 15ml and the mixture was stirred at room temperature for 45 minutes. To the obtained crude substance in methanol (10ml) were added sodium cyanoborohydride 280mg (4.24mmol) and methyl 3-(formylphenyl)-acetate 228mg (1.28mmol) at room temperature, and the mixture was stirred at room temperature for 21 hours. After removal of the solvent by distillation, thereto was added saturated brine 50ml and the mixture was extracted with 33% ethanol-chloroform (150ml). The organic layer was dried over anhydrous magnesium sulfate, concentrated in vacuo and purified by silica gel column chromatography to give the subtitled compound 316mg as a colorless oil. Yield 67% 1H NMR (CDCl3) delta 7.32-7.14 (4H, m), 5.19 (2H, brs), 4.43 (2H, t, J= 4.9 Hz), 4.10 (3H, s), 3.84 (2H, d, J= 7.2 Hz), 3.75 (2H, t, J= 4.9 Hz), 3.68 (3H, s), 3.63 (2H, s), 3.38 (3H, s), 2.44-2.40 (2H, m), 2.24 (3H, s), 2.30-1.80 (11H, m), 1.70-1.60 (2H, m).

Reference： [1]Patent: EP1939199,2008,A1 .Location in patent: Page/Page column 38

53
[ 930778-13-5 ]
[ 142327-44-4 ]
[ 930777-49-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; In methanol; at 20℃;	Step (ix); Methyl {3-[({1-[2-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)ethyl]piperidin-4-yl}amino)methyl]phenyl}acetate; The compound (400mg) obtained in step (viii), methyl (3-formylphenyl)-acetate (204mg) and sodium triacetoxyborohydride (730mg) were dissolved in methanol (10ml), and the solution was stirred at room temperature overnight. The reaction mixture was treated with SCX, and purified by reverse-phase HPLC to give the titled compound. Yield 96mg 1H NMR delta (DMSO-d6) 7.25 - 7.07 (4H, m), 6.37 (2H, brs), 4.14 (2H, J = 6.8 Hz, t), 3.75 (2H, J = 6.4 Hz, t), 3.66 (2H, s), 3.64 (2H, s), 3.60 (3H, s), 2.85 (2H, m), 2.55 - 2.32 (3H, m), 1.96 - 1.12 (10H, m), 0.92 (3H, J = 7.2 Hz, t). MS: APCI (+ve): 512 (M+H)

Reference： [1]Patent: EP1939199,2008,A1 .Location in patent: Page/Page column 92

54
[ 930777-63-2 ]
[ 142327-44-4 ]
[ 930777-64-3 ]

Yield	Reaction Conditions	Operation in experiment
68%		Step (iv); 2-Butoxy-9-[2-(3-{N-[(3-methoxycarbonylmethylphenyl-1-yl)methyl]-N-methylamino}propyl)piperidin-4-yl]methyl}-8-methoxyadenine; [Show Image] To the compound 181mg (0.357mmol) obtained in step (iii) was added trifluoroacetic acid 5ml and the mixture was stirred at room temperature for 35 minutes. After removal of the solvent by distillation, to the residue was added aqueous saturated sodium bicarbonate 20ml and the mixture was extracted with 33% ethanol-chloroform (50ml x 3). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. To the resulting crude product in methanol (5ml) were added sodium cyanoborohydride 96.7mg (1.46mmol) and methyl 3-formyl-phenyl-acetate 77.1mg (0.432mmol) at room temperature, and the mixture was stirred at room temperature for 4 days. After removal of the solvent by distillation, to the residue was added saturated brine 5ml and the mixture was extracted with 33% ethanol-chloroform (10ml x 3). The organic layer was dried over anhydrous magnesium sulfate, concentrated in vacuo and purified by silica gel column chromatography to give the subtitled compound 138mg as a colorless oil. Yield 68% 1H NMR (CDCl3) delta7.30-7.14 (4H, m), 5.22 (2H, bs), 4.27 (2H, t, J= 6.7 Hz), 4.10 (3H, s), 3.81 (2H, d, J= 7.3 Hz), 3.69 (3H, s), 3.61 (3H, s), 3.45 (2H,s), 2.93-2.86 (2H, m), 2.39-2.30 (4H, m), 2.17 (3H, s), 1.93-1.68 (10H, m), 1.60-1.30 (6H, m), 0.96 (3H, t, J= 7.4 Hz).

Reference： [1]Patent: EP1939199,2008,A1 .Location in patent: Page/Page column 31-32

55
[ 930777-65-4 ]
[ 142327-44-4 ]
[ 930777-66-5 ]

Yield	Reaction Conditions	Operation in experiment
33%		Step (ii) 2-Butoxy-9-[2-(3-{N-[(3-methoxycarbonylmethylphenyl-1 - yl)methyl]amino}propyl)piperidin-4-yl]methyl}-8-methoxyadenine; [Show Image] To the compound 292mg (0.559mmol) obtained in step (i) in ethanol (10ml) was added hydrazine monohydrate (1ml) and the mixture was refluxed for 30 minutes. After being cooled to room temperature, the resulting solid was filtered off. After removal of the solvent by distillation, to the residue, was added aqueous saturated sodium bicarbonate 30ml and the mixture was extracted with 33% ethanol-chloroform (150ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. To the obtained crude product in methanol (6ml) were added sodium cyanoborohydride 178mg (2.69mmol) and methyl (3-formylphenyl)acetate 105mg (0.588mol) at room temperature, and the mixture was stirred at room temperature for 45 hours. After removal of the solvent by distillation, to the residue was added saturated brine 6ml and the mixture was extracted with 33% ethanol-chloroform (45ml). The organic layer was dried over anhydrous magnesium sulfate, concentrated in vacuo and purified by silica gel column chromatography to give the subtitled compound 97.7mg as a colorless oil. Yield 33% 1H NMR (CDCl3) delta 7.36-7.18 (4H, m), 5.14 (2H, brs), 4.26 (2H, t, J = 6.7 Hz), 4.10 (3H, s), 3.87 (2H, brs), 3.76 (2H, d, J= 7.3 Hz), 3.69 (3H, s), 3.64 (2H, s), 3.00-2.94 (2H, m), 2.84-2.78 (2H, m), 2.47-2.41 (2H, m), 1.93-1.70 (7H, m), 1.60-1.42 (4H, m), 1.34-1.23 (2H, m), 0.96 (3H, t, J = 7.4 Hz).

Reference： [1]Patent: EP1939199,2008,A1 .Location in patent: Page/Page column 33-34

56
[ 930785-10-7 ]
[ 142327-44-4 ]
[ 930785-11-8 ]

Yield	Reaction Conditions	Operation in experiment
58%		Step (iv); 2-Butoxy-9-([3-{N-[3-(methoxycarbonylmethyl)benzyl]amino}propoxy]benzyl)-8-methoxyadenine; [Show Image] The compound 0.20g (0.51mmol) obtained in step (ii) and the compound 0.14g (0.76mmol) obtained in step (iii) were dissolved in methanol 10ml and the solution was stirred at room temperature for 1 hour. Thereto was added sodium cyanoborohydride 0.13g (2.5mmol), followed by stirring for 15 hours. Thereto was added acetic acid 0.85ml (15mmol) and the mixture was stirred for 10 minutes. After removal of the solvent, to the residue was added aqueous sodium hydrogencarbonate and the mixture was extracted with chloroform/ethanol (3/ 1). The organic layer was dried over anhydrous magnesium sulfate, concentrated in vacuo and the residue was purified by silica gel column chromatography to give the object compound 0.17g as a colorless oil. Yield 58% 1H NMR (CDCl3) delta7.30-7.15 (6H, m), 6.80 (2H, d, J = 8.7 Hz), 5.23 (2H, brs), 5.02 (2H, s), 4.30 (2H, t, J = 6.7 Hz), 4.08 (3H, s), 4.00 (2H, t, J = 6.1 Hz), 3.79 (2H, s), 3.67 (3H, s), 3.60 (2H, s), 2.81 (2H, t, J = 6.9 Hz), 2.00 (1H, brs), 1.97 (2H, tt, J = 6.9 Hz, 6.1 Hz), 1.77 (2H, tt, J = 7.5 Hz, 6.7 Hz), 1.51 (2H, tq, J = 7.5 Hz, 7.4 Hz), 0.97 (3H, t, J = 7.4 Hz).

Reference： [1]Patent: EP1939202,2008,A1 .Location in patent: Page/Page column 34

57
[ 823809-16-1 ]
[ 142327-44-4 ]
[ 1080007-50-6 ]

Yield	Reaction Conditions	Operation in experiment
		v) Methyl 2-(3-((3-(4-amino-2-(ethoxymethyl)-lH-imidazo[4,5-c]quinolin-l- yl)propylamino)methyl)phenyl)acetate; Methyl 2-(3-formylphenyl)acetate (199mg) was added to the product of step (iv) (334mg) in THF (2OmL) at 25C under nitrogen. The resulting solution was stirred at rt for 6h. Sodium triacetoxyborohydride (1183mg) was added to the reaction mixture at rt under nitrogen and the mixture was stirred at rt for 15h. The reaction mixture was quenched with water and dissolved in MeOH. The product was purified via RPHPLC, which afforded25mg of the desired product as a white solid.MS APCI +ve: 462

Reference： [1]Patent: WO2008/135791,2008,A1 .Location in patent: Page/Page column 57

58
[ 1080007-58-4 ]
[ 142327-44-4 ]
[ 1080007-55-1 ]

Yield	Reaction Conditions	Operation in experiment
		ii) Methyl 2-(3-(((3-(4-amino-2-butyl-lH-imidazo[4,5-c]quinolin-l-yl)propyl)(l- methylpiperidin-4-yl)amino)methyl)phenyl)acetate; A solution of <strong>[142327-44-4]methyl 2-(3-formylphenyl)acetate</strong> (0.15g) dissolved in NMP (1OmL) was added to a stirred solution of the product from step (i) (0.36g) in NMP (1OmL) at rt. Sodium triacetoxyborohydride (0.9Og) was added to the mixture, the temperature was increased to 500C and the reaction mixture stirred for 24h. The resulting solution was dissolved in methanol (0.5mL), acidified with acetic acid (0.5mL) and purified by SCX. The crude product was further purified by RPHPLC to give the title product, yield 22mg. 1H NMR delta (DMSO-de) 7.95 (IH, d) ; 7.59 (IH, d) ; 7.38 (IH, m) ; 7.27-7.04 (5H, m) ; 6.41 (2H, brs); 4.34 (2H, m) ; 3.62 (3H, m) ; 3.50 (2H, s) ; 3.29 (3H, s) ; 2.90-2.65 (4H, m) ; 2.30-2.40 (4H, m) ; 1.85-1.24 (9H, m) ; 0.92 (3H, t) MS: APCI (+ve): 557

Reference： [1]Patent: WO2008/135791,2008,A1 .Location in patent: Page/Page column 58

59
[ 259680-82-5 ]
[ 142327-44-4 ]
[ 1158802-26-6 ]

Yield	Reaction Conditions	Operation in experiment
		(vi) Methyl 2-(3-((3-(2-Ammo-4-methyl-6-(pentylamino)pyrimidin-5- yl)propylamino)methyl) phenyl)acetateThe product from step (v) (Ig) was dissolved in THF (3OmL) then acetic acid (0.239g, 0.23ml) and <strong>[142327-44-4]methyl 2-(3-formylphenyl)acetate</strong> (0.709g) were added followed by MeOH (0.5mL). The reaction mixture was stirred at rt for 72h then sodium borohydride (0.1506g) was added. After 2h a further portion of sodium borohydride (0.0452g) was added and the reaction mixture stirred for 16h. A further portion of sodium borohydride (0.1506g) was added and stirred for 2h. The reaction mixture was poured into saturated sodium bicarbonate solution and extracted with EtOAc. The solvents were evaporated and the product was purified by chromatography eluting with DCM:MeOH 97:3 to 80:20 to give the title compound 0.5g.1H NMR (DMSO-Jo): delta 7.31 - 7.18 (m, 3H), 7.12 (d, IH), 6.54 (t, IH), 5.48 (d, 2H), 3.65 (d, 4H), 3.60 (s, 3H), 3.27 - 3.17 (m, 2H), 2.49 - 2.44 (m, 2H), 2.35 (t, 2H), 2.05 (s, 3H), 1.55 - 1.39 (m, 4H), 1.29 - 1.16 (m, 4H), 0.84 (t, 3H) LC-MS m/z 414 ESI

Reference： [1]Patent: WO2009/67081,2009,A1 .Location in patent: Page/Page column 66

60
[ 1158803-93-0 ]
[ 142327-44-4 ]
[ 1158802-42-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; acetic acid; In tetrahydrofuran; for 72h;	(iii) Methyl 2-(3-((4-(2-amino-4-methyl-6-(pentylamino)pyrimidin-5- yl)butylamino)methyl)phenyl)acetateTo the product of step (ii) (0.06g), <strong>[142327-44-4]methyl 2-(3-formylphenyl)acetate</strong> (0.0403g) and acetic acid (0.0136g) in THF (1OmL) was added sodium triacetoxyborohydride (0.1102g). The reaction mixture was stirred for 72h, the solvents were evaporated and the residue dissolved in MeOH, acidified and purified via SCX resin, then RPHPLC to give the title compound 6mg. LC-MS m/z 428 ESI

Reference： [1]Patent: WO2009/67081,2009,A1 .Location in patent: Page/Page column 78

61
6-Amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-7,9-dihydro-8H-purine-8-one dimaleate [ No CAS ]
[ 142327-44-4 ]
[ 866269-28-5 ]

Yield	Reaction Conditions	Operation in experiment
		Example 5 Methyl (3-[[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purin-9-yl)propyl](3-morpholin-4-ylpropyl)amino]methyl}phenyl)acetate To a suspension of 6-amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-8-oxo-7,9-dihydro-8H-purine dimaleate (15.00g, 23.45mmol) in NMP (54.08g) was added triethyamine (7.12g, 70.35mmol) at 25C. Then sodium acetoxyborohydride (8.45g, 39.87mmol) was added thereto, followed by stirring at 25C for 15 minutes. After adding methyl (3-formylphenyl)acetate (6.27g, 35.18mol) and stirring at 25C for 8 hours, the mixture was cooled to 5C and then diluted with cold water (240.00). After adjusting pH to 7 with 10% sodium carbonate solution, a seed crystal was added thereto. After stirring for additional 15 minutes, the mixture was adjusted to pH 8 with 10% sodium carbonate solution and thereto was added water (15g). After keeping at 5C for 1 hour, the resulting white solid was filtered, washed and dried to give the subject compound (12.10g, 90.6%). The seed crystal used in the above was obtained by the method of the above example 5 without adding a seed crystal as the method of the above Example 5. Purity: 94.81% (HPLC) 1H NMR (DMSO-d6) delta 9.82 (1H, bs), 7.24-7.15 (3H, m), 7.10 (1H, d, J = 7.3 Hz), 6.39 (2H, bs), 4.11 (2H, t, J = 6.6 Hz), 3.67 (2H, t, J = 7.2 Hz), 3.64 (2H, s), 3.59 (3H, s), 3.46-3.49 (6H, m), 2.41-2.34 (4H, m), 2.22-2.16 (6H, m), 1.85-1.80 (2H, m), 1.65-1.57 (2H, m), 1.52-1.45 (2H, m), 1.40-1.31 (2H, m), 0.89 (3H, t, J = 7.4 Hz). m.p.: 152.7C

Reference： [1]Patent: EP2246353,2010,A1 .Location in patent: Page/Page column 16

62
6-amino-2-butoxy-9-{3-[((3-morpholin-4-ylpropyl)amino)]propyl}-7,9-dihydro-8H-purine-8-one dimalonate [ No CAS ]
[ 142327-44-4 ]
[ 866269-28-5 ]

Yield	Reaction Conditions	Operation in experiment
95.7%		Example 8 Methyl (3-[[3-(6-amino-2-butoxy-8-oxo-7.8-dihydro-9H-purin-9-yl)propyl](3-morpholin-4-ylpropyl)amino]methyl}phenyl) acetate To a suspension of 6-amino-2-butoxy-9-{3-(3-morpholin-4-ylpropyl)amino)]propyl}-7,9-dihidro-8H-purine-8-one dimalonate (2.80g, 4.55mmol) in NMP (11.5g) was added at 25C triethyamine (1.38g, 13.64mmol). After stirring for 10 minutes, thereto was added sodium triacetoxyborohydride (1.64g, 7.73mmol), and the mixture was stirred at 25C for 10 minutes. After adding methyl (3-formylphenyl)acetate (1.42g, 7.96mmol) and stirring at 25C for 8 hours, thereto was added NMP (11.5g) and the mixture was cooled to 5C, followed by being quenched with cold water 45 g. The solution was adjusted to pH7 with 10% sodium carbonate solution, and thereto was added a seed crystal (10mg, 0.017mmol). After stirring for 15 minutes, the solution was adjusted to pH 8 with 10% sodium carbonate solution and thereto was added water. After keeping at 5C for 1 hour, the resulting crystal was filtered, washed and dried to give the subject compound (2.48 g, 95.7%). 1H NMR (DMSO-d6) delta 9.82 (1H, bs), 7.24-7.15 (3H, m), 7.10 (1H, d, J = 7.3 Hz), 6.39 (2H, bs), 4.11 (2H, t, J = 6.6 Hz), 3.67 (2H, t, J = 7.2 Hz), 3.64 (2H, s), 3.59 (3H, s), 3.46-3.49 (6H, m), 2.41-2.34 (4H, m), 2.22-2.16 (6H, m), 1.85-1.80 (2H, m), 1.65-1.57 (2H, m), 1.52-1.45 (2H, m), 1.40-1.31 (2H, m), 0.89 (3H, t, J = 7.4 Hz).

Reference： [1]Patent: EP2246353,2010,A1 .Location in patent: Page/Page column 19

63
6-amino-2-butoxy-9-{3-[(3-morpholin-4-ylpropyl)amino]propyl}-7,9-dihydro-8H-purine-8-one trihydrochloride [ No CAS ]
[ 142327-44-4 ]
[ 866269-28-5 ]

Yield	Reaction Conditions	Operation in experiment
89%		Example 10Methyl (3-[[3-(6-amino-2-butoxy-8-oxo-7,8-dihydro-9H-purine-9-yl)propyl](3-morpholin-4-ylpropyl)amino]methyl}phenyl acetate To a solution of the compound prepared by example 9 (1.00 g, 1.93 mmol) in N-methyl-2-pyrrolidine (10 ml) were added triethylamine (1.14 ml, 7.73 mmol) and methyl (3-formylphenyl)acetate (0.52 g, 2.90 mmol), and the mixture was stirred at room temperature for 0.5 hour. Thereto was added sodium triacetoxyborohydride (0.82 g, 3.87 mmol), and the mixture was further stirred for 24 hours. Thereto was added water and the solution was adjusted to pH8 with a diluted aqueous ammonium solution. The resulting crystal was filtered to give the subject compound (0.98 g, 89%).1H NMR delta (DMSO-d6) 9.82 (1H, bs), 7.24-7.15 (3H, m), 7.10 (1H, d, J=7.3 Hz), 6.39 (2H, bs), 4.11 (2H, t, J=6.6 Hz), 3.67 (2H, t, J=7.2 Hz), 3.64 (2H, s), 3.59 (3H, s), 3.46-3.49 (6H, m), 2.41-2.34 (4H, m), 2.22-2.16 (6H, m), 1.85-1.80 (2H, m), 1.65-1.57 (2H, m), 1.52-1.45 (2H, m), 1.40-1.31 (2H, m), 0.89 (3H, t, J=7.4 Hz).

Reference： [1]Patent: US2011/54168,2011,A1 .Location in patent: Page/Page column 10-11

64
1-(4-aminobutyl)-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin4-amine [ No CAS ]
[ 142327-44-4 ]
[ 1382350-80-2 ]

Yield	Reaction Conditions	Operation in experiment
		A solution of the product from step (v) (1. lg) in MeOH (30mL) was treated with acetic acid (0.37mL) followed by <strong>[142327-44-4]methyl 2-(3-formylphenyl)acetate</strong> (0.6 lg) and was stirred at rt for 20 mins and then cooled in an ice bath. Sodium cyanoborohydride (0.4 lg) was added and the reaction mixture was stirred at rt for 3 hours. The solvent was evaporated under reduced pressure and the residue partitioned between EtOAc and sodium bicarbonate solution. The organic layer was evaporated under reduced pressure and the crude product was purified by silica chromatography to give the subtitle compound as a solid (1.16g); MS multimode (+) 476; 1H NMR (500 MHz, DMSO) delta 9.41 (s, 2H), 8.95 (s, 2H), 8.74 (dd, IH), 8.17 (dd, IH), 7.75 (dd, IH), 7.46 - 7.28 (m, 4H), 4.94 - 4.74 (m, 4H), 4.14 (s, 2H), 3.68 (s, 2H), 3.65 - 3.35 (m, 5H), 3.00 (s, 2H), 2.04 - 1.87 (m, 2H), 1.81 - 1.67 (m, 2H), 1.18 (t, 3H).

Reference： [1]Patent: WO2012/80728,2012,A1 .Location in patent: Page/Page column 33-34

65
(R)-(1-(6-amino-5-nitropyridin-2-yl)piperidin-3-yl) (pyrrolidin-1-yl)methanone [ No CAS ]
[ 142327-44-4 ]
(R)-methyl 2-(3-(5-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)phenyl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 1 10: if?)-Methyl 2-(3-(5-(3-(pyrrolidine-1-carbonyl)piperidin-1-yl)-3/-/- imidazo[4,5-blpyridin-2-yl)phenyl)acetate Into a vial was added <strong>[142327-44-4]methyl 2-(3-formylphenyl)acetate</strong> (98 mg, 0.55 mmol), (R)-^-{6- amino-5-nitropyridin-2-yl)piperidin-3-yl)(pyrrolidin-1 -yl)methanone (Intermediate 1 , Step 3) (140 mg, 0.45 mmol) and ethanol (1.5 ml_). Then sodium dithionate (388 mg, 2.23 mmol) and water (0.5 ml.) were added to the mixture. The vial was sealed. The reaction mixture was heated to 1 10C for 18 h. The solution was cooled to room temperature. Triethylamine (0.15 ml_, 1.1 mmol) was added and the solution was stirreed at 100C for 18 h. A sample (0.8 ml.) of the solution was removed and concentrated to dryness, and the resulting residue was purified via HPLC to afford the title compound. MS (ESI+)(M+H) 448.2; HPLC retention time 2.28 min (Method A).

Reference： [1]Patent: WO2013/150416,2013,A1 .Location in patent: Page/Page column 165

66
[ 142327-44-4 ]
[ 374898-01-8 ]
C₁₈H₂₀FNO₂ [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 419 - 424

67
[ 142327-44-4 ]
C₂₈H₂₅FN₂O₃ [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 419 - 424

68
[ 142327-44-4 ]
C₂₇H₂₃FN₂O₃ [ No CAS ]

Reference： [1]ACS Medicinal Chemistry Letters,2015,vol. 6,p. 419 - 424

69
[ 142327-44-4 ]
(3-(((4-butyl-benzyl)-(1-methyl-1 H-imidazole-4-sulfonyl)-amino)-methyl)-phenyl)-acetic acid [ No CAS ]

Reference： [1]Patent: US6498172,2002,B1

70
[ 142327-44-4 ]
[ 223490-91-3 ]

Reference： [1]Patent: US6498172,2002,B1

71
[ 2038-57-5 ]
[ 142327-44-4 ]
[ 950502-93-9 ]