620611-27-0|tert-Butyl 4-(aminomethyl)-4-fluoropiperidine-1-carboxylate| Ambeed

Structure of 620611-27-0

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Quality Control of [ 620611-27-0 ] Purity: 97% SDS Specification

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Product Details of [ 620611-27-0 ]

CAS No. :	620611-27-0
Formula :	C₁₁H₂₁FN₂O₂
M.W :	232.30
SMILES Code :	O=C(N1CCC(F)(CN)CC1)OC(C)(C)C
MDL No. :	MFCD11847970
InChI Key :	FCYNTMBZASDPHJ-UHFFFAOYSA-N
Pubchem ID :	40152119

Safety of [ 620611-27-0 ]

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

Computational Chemistry of [ 620611-27-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	16
Num. arom. heavy atoms	0
Fraction Csp3	0.91
Num. rotatable bonds	4
Num. H-bond acceptors	4.0
Num. H-bond donors	1.0
Molar Refractivity	64.2
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	55.56 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.51
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	0.89
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.72
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.3
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.12
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.51

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.58
Solubility	6.15 mg/ml ; 0.0265 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.64
Solubility	5.3 mg/ml ; 0.0228 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-1.82
Solubility	3.48 mg/ml ; 0.015 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.09 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.38

Application In Synthesis of [ 620611-27-0 ]

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

Downstream synthetic route of [ 620611-27-0 ]

[ 620611-27-0 ] Synthesis Path-Downstream 1~35

1
[ 620611-27-0 ]
[ 161622-05-5 ]
[ 918431-91-1 ]

Yield	Reaction Conditions	Operation in experiment
		te?'/-butyl 4-fluoro-4-rf3-fluoro-5-('trifluoromethyl')benzamido')methyl)piperidine-l-carboxylate (3-5'); 1-Hydrozybenzotriazole (0.973 g, 7.2 mmol) and 3-fluoro-5-(trifluoromethyl)benzoic acid (1.25 g, 6.0 mmol) were suspended in 30 mL diy CH2Cl2. Diisopropylethylamine (2.1 mL, 12.0 mmol) was added and all compounds went into solution. Amine 3-4 (1.39 g, 6.0 mmol) was added in 30 mL dry CH2Cl2. PS-carbodiimide resin (7.5 g, 12.0 mmol) was then added and the mixture was vigorously stirred overnight. MP-carbonate resin (4.Og, 12.0 mmol) was added and stirring was resumed for 3 h. The reaction was then filtered to remove resin and concentrated in vacuo. A 40 g SiO2 column was run in 0-50% EtOAc/hexanes, yielding 902 mg of 3-5 (36% over 3 steps) as a viscous yellow oil. 1H NMR (CDCl3, 300 MHz): 7.84 (s, IH), 7.73 (d, J= 8.4 Hz, IH), 7.45 (d, J= 8.4 Hz, IH), 3.92 (br, 2H), 3.65 (m, 2H), 3.10 (m, 2H), 1.68 (m, 4H), 1.43 (s, 9H); MS (Electrospray): m/z 445.2 (M+Na), 367.1 (M- t-Bu+H).

References: [1]Patent: WO2007/2884,2007,A2 .Location in patent: Page/Page column 24.

2
[ 918431-93-3 ]
[ 620611-27-0 ]

Yield	Reaction Conditions	Operation in experiment
		tert-butyl 4-(aminomethyl)-4-fluoropiperidine-l-carboxylate (4-4); To a 0 C solution of 4-3 (8.83 g, 38.7 mmol) in 75 mL dry THF was added a solution of 1 M borane in THF (155 mL, 155 mmol) over 30 min. After 30 min more, the cold reaction was slowly quenched with EtOH (200 mL) and all solvent was removed in vacuo. The residue was taken up in saturated aq. NHtCl/EtOAc (150 mL) and extracted with EtOAc (3 x 150 mL). The organic layers were washed with 1 N aq. NaOH, brine, dried over MgSO4, filtered, and concentrated in vacuo, giving crude 4-4 as a pale yellow oil. The crude amine 4-4 was carried forward. 1H NMR (CDCl3, 300 MHz): 3.94 EPO <DP n="27"/>(br, 2H), 3.08 (m, 2H), 1.85 (m, 2H), 1.51 (m, 4H), 1.44 (s, 9H); MS (Electrospray): m/z 218.2 (M-Me+H), 177.2 (M-f-Bu+H).

References: [1]Organic and Biomolecular Chemistry,2010,vol. 8,p. 2509 - 2512.
[2]Journal of Medicinal Chemistry,2008,vol. 51,p. 3692 - 3695.
[3]Patent: WO2007/2884,2007,A2 .Location in patent: Page/Page column 25-26.

3
[ 620611-27-0 ]
[ 51-36-5 ]
[ 918431-94-4 ]

Yield	Reaction Conditions	Operation in experiment
		fe/Y-butyl 4-((3 ,5-dichlorobenzamido)methyl)-4-fluoropiperidine- 1 -carboxylate (4-5); 1-Hydroxybenzotriazole (6.27 g, 46.4 mmol) and 3,5-dichlorobenzoic acid (8.13 g, 42.6 mmol) were suspended in 210 mL dry CH2Cl2. Diisopropylethylamine (13.5 mL, 77.4 mmol) was added and all compounds went into solution. Amine 4-4 (10.4 g crude, 38.7 mmol) was added in 210 mL dry CH2CI2. PS-carbodiimide resin (59.5 g, 77.4 mmol) was then added and the mixture was stirred for 14 h. MP-carbonate resin (41.8 g, 120 mmol) was added and stirring was resumed for 3 h. The reaction was then filtered to remove resin and concentrated in vacuo, yielding 22.2 g of crude 4-5 as a viscous yellow oil. The crude amide 4-5 was carried forward. 1HNMR (CDCl3, 300 MHz): 7.94 (d, J= 1.8 Hz, IH),7.66 (d, J= 1.8 Hz, 2H), 6.44 (br t, IH)5 3.93 (br, 2H), 3.65 (br, 2H), 3.12 (br t, 2H), 1.83 (br t, 2H), 1.67 (m, 2H), 1.46 (s, 9H); MS (Electrospray): m/z 427.1 (M+Na), 349.1 (M-t-Bu+H).

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 3692 - 3695.
[2]Patent: WO2007/2884,2007,A2 .Location in patent: Page/Page column 26.

4
methyl 3,4-diaminobenzoate dihydrochloride [ No CAS ]
[ 620611-27-0 ]
[ 620611-29-2 ]

Yield	Reaction Conditions	Operation in experiment
60%		[Reference Example 4] Synthesis of 4-fluoro-4-([5-(methoxycarbonyl)benzimidazol-2-yl]amino}methyl)piperidinecarboxylic acid tert-butyl ester 4-(Aminomethyl)-4-fluoropiperidinecarboxylic acidtert-butyl ester (3.23 g, 13.9 mmol) was dissolved in acetonitrile (50 ml). A solution of thiocarbonyldiimidazole (2.73 g, 15.3 mmol) and triethylamine (4.27 ml, 30.6 mmol) in acetonitrile (20 ml) was then added dropwise at 0C of a period of 3 minutes. After stirring at room temperature for 1 hour, 3,4-diaminobenzoic acid methyl ester dihydrochloride (3.66 g, 15.3 mmol) was added to the reaction mixture, and the mixture was stirred at 50C for 5.5 hours. Diisopropylcarbodiimide (0.32 ml, 15.3 mmol) was further added and the mixture was stirred overnight at 50C. Saturated brine was added to the obtained reaction mixture, extraction was performed with ethyl acetate (200 ml), and the organic layer was dried overnight over anhydrous sodium sulfate. After filtration with a desiccant (anhydrous sodium sulfate) and concentration of the filtrate, the obtained brown oil was purified by silica gel column chromatography (CH2Cl2/MeOH = 49:1 ? 19:1) to obtain 4-fluoro-4-([5-(methoxycarbonyl)benzimidazol-2-yl]amino}methyl)piperidinecarboxylic acid tert-butyl ester. The yield was 0.838 g (60%). 1H-NMR (270 MHz, CDCl3): delta1.43-1.95(m,5H), 1.45(s,9H), 3.06(brt,2H,J=11.3Hz), 3.50(s,3H), 3.67(d,2H,J=21.6Hz), 3.83-3.96(m,2H), 3.90(s,2H), 7.28(d,1H,J=8.4Hz), 7.81(dd,1H,J=1.6,8.4Hz), 7.90(brs,1H).

References: [1]Patent: EP1505067,2005,A1 .Location in patent: Page/Page column 369.

5
[ 620611-27-0 ]
[ 199915-38-3 ]
4-[([(fluoren-9-ylmethoxy)carbonylamino]thioxomethyl}amino)methyl]-4-fluoropiperidinecarboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In tetrahydrofuran; at 20℃;	[Reference Example 6] Synthesis of 4-[([(fluoren-9-ylmethoxy)carbonylamino] thioxomethyl}amino)methyl]-4-fluoropiperidinecarboxylic acid tert-butyl ester After dissolving <strong>[620611-27-0]4-(aminomethyl)-4-fluoropiperidinecarboxylic acid tert-butyl ester</strong> (1071 mg, 4.61 mmol) in tetrahydrofuran (10 ml), FmocNCS (9-fluorenylmethoxycarbonyl isothiocyanate) (1425 mg, 5.07 mmol) was added and the mixture was stirred at room temperature overnight. After completion of the reaction, the mixture was concentrated and purified by silica gel column chromatography (hexane/ethyl acetate = 10/1-5/1) to obtain 4-[([(fluoren-9-ylmethoxy)carbonylamino] thioxomethyl}amino)methyl]-4-fluoropiperidinecarboxylic acid tert-butyl ester. The compound was identified by LC-MS. Yield: 1896 mg (80%), M+1 = 514.2

References: [1]Patent: EP1505067,2005,A1 .Location in patent: Page/Page column 370.

6
[ 620611-27-0 ]
[ 1992-90-1 ]
[ 620611-46-3 ]

Yield	Reaction Conditions	Operation in experiment
69%		[Reference Example 36] Synthesis of 4-fluoro-4-[(7-fluoro-1,1-dioxo-4H-benzo[e]1,2,4-thiadiazine-3-yl)amino]methyl}piperidinecarboxylic acid tert-butyl ester The 4-(aminomethyl)-4-fluoropiperidinecarboxylic acidtert-butyl ester (1.0 g, 4.30 mmol) synthesised in Reference Example 3 was dissolved in acetonitrile (30.0 mL), and the solution was cooled to 0C. A solution of 1,1'-thiocarbonyldiimidazole (844 mg, 4.73 mmol) and imidazole (88 mg, 1.30 mmol) in acetonitrile (10 mL) was added dropwise thereto, and the mixture was stirred at room temperature for 2 hours. Next, 2-amino-5-fluorobenzenesulfonamide (981 mg, 5.16 mmol) and dimethylaminopyridine (630 mg, 5.16 mmol) were added to the reaction mixture which was then stirred at 80C overnight. Diisopropylcarbodiimide (0.662 mL, 4.30 mmol) was added thereto, and the mixture was stirred for 1 hour. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (50 mL). This was washed with water (20 mL) and saturated brine (20 mL), and then dried over anhydrous sodium sulfate. The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (n-hexane:ethyl acetate = 3:2 ? 2:3) to obtain 4-fluoro-4-[(7-fluoro-1,1-dioxo-4H-benzo[e]1,2,4-thiadiazine-3-yl)amino]methyl}piperidinecarboxylic acid tert-butyl ester. Yield: 1.27 g (69%), M-Boc+2H = 331.1.

References: [1]Patent: EP1505067,2005,A1 .Location in patent: Page/Page column 380.

7
[ 620611-28-1 ]
[ 620611-27-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine; In ethanol; at 20℃; for 2h;	After dissolving 4-fluoro-4-(hydroxymethyl)piperidinecarboxylic acid tert-butyl ester (4.26 g, 18.3 mmol) in THF (183 mL), the solution was cooled to 0C. Triphenylphosphine (7.19 g, 27.4 mmol) and DIAD (diisopropyl azodicarboxylate) (5.39 mL, 27.4 mmol) were then added to the solution. After stirring for 20 minutes, phthalimide (4.03 g, 27.4 mmol) was added and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was concentrated, and the crude product was crudely purified by silica gel column chromatography (20% AcOEt/hexane) to obtain 4-[(1,3-dioxoisoindolin-2-yl)methyl]-4-fluoropiperidinecarboxylic acid tert-butyl ester. The 4-[(1,3-dioxoisoindolin-2-yl)methyl]-4-fluoropiperidinecarboxylic acid tert-butyl ester was dissolved in ethanol (200 mL), and then hydrazine monohydrate (10.0 mL) was added. After stirring at room temperature for 2 hours, the precipitated solid was filtered out and the filtrate was concentrated under reduced pressure. The obtained crudely purified product was further purified by silica gel column chromatography (5% MeOH/CH2Cl2) to obtain 4-(aminomethyl)-4-fluoropiperidinecarboxylic acid tert-butyl ester. The compound was identified by 1H-NMR. The yield was 3.23 g (76%). 1H-NMR (270 MHz, CDCl3): 1.36-1.70(m,4 H), 1.46(s,9H), 1.80-1.93(m,2H), 2.79(d,2H,J=20.3Hz), 3.08(brt,2H,J=11.0Hz), 3.95(brd,2H,J=11.0Hz).
	With ethanolamine; at 60℃; for 1h;Product distribution / selectivity;	fe?t-butyl 4-(aminomethyl)-4-fluoropiperidine-l-carboxylate (3-4); A mixture of 3-3 (ll.Og) and 25 mL ethanolamine was stirred at 60 C for 1 h. The reaction was then allowed to cool to room temperature, poured into ice- water (100 mL), and extracted with CH2Cl2 (3 x 100 mL). The combined organic layers were washed with brine (150 mL), dried over MgSO4, filtered, and concentrated in vacuo, giving 5.82 g of crude 3-4 as a viscous amber oil. 1H NMR EPO <DP n="25"/>(CDCl3, 300 MHz): 3.94 (br, 2H), 3.08 (m, 2H), 1.85 (m, 2H), 1.51 (m, 4H), 1.44 (s, 9H) ; MS (Electrospray): m/z 218.2 (M-Me+H), 177.2 (M-t-Bu+H).
	With ethanolamine; at 60℃; for 2.5h;	The crude product from Step C (2.45 g) was suspended in 6 mL of ethanolamine and heated at 60 C. for 2.5 h. After cooling at room temperature, water (50 mL) was added and the mixture was extracted with ethyl acetate (3×250 mL). The organic phase was dried over Na2SO4, filtered and the solvent was removed. The residue was purified using a Biotage flash chromatography system (methanol/dichloromethane: 20-50%) to give a yellowish oil (0.670 g, 46% for 3 steps).1H-NMR (400 MHz, CDCl3): =3.94 (brs, 2H), 3.06 (m, 2H), 1.84 (m, 2H), 1.56 (m, 4H), 1.44 (s, 9H).MS (ESI): m/z=177.04 (M-t-Bu+H)+, 217.96 (M-Me+ H)+, 233.01 (MH)+.

With ethanolamine; at 60℃; for 2.5h;

Step D The crude product from Step C (2.45 g) was suspended in 6 mL of ethanolamine and heated at 60C for 2.5h. After cooling at room temperature, water (50 mL) was added and the mixture was extracted with ethyl acetate (3 X 250 mL). The organic phase was dried over Na2SO4, filtered and the solvent was removed. The residue was purified using a Biotage flash chromatography system (methanol/dichloromethane: 20-50%) to give a yellowish oil (0.670 g, 46% for 3 steps). 1H-NMR (400 MHz, CDCl3): delta = 3.94 (brs, 2H), 3.06 (m, 2H), 1.84 (m, 2H), 1.56 (m, 4H), 1.44 (s, 9H) MS (ESI): m/z = 177.04 (M-t-Bu+H)+, 217.96 (M-Me+H)+, 233.01 (MH)+

References: [1]Patent: EP1505067,2005,A1 .Location in patent: Page/Page column 369.
[2]Journal of Medicinal Chemistry,2008,vol. 51,p. 3692 - 3695.
[3]Patent: WO2007/2884,2007,A2 .Location in patent: Page/Page column 23-24.
[4]Patent: US2011/256064,2011,A1 .Location in patent: Page/Page column 20.
[5]Patent: EP2377860,2011,A1 .Location in patent: Page/Page column 27.

8
[ 1228765-02-3 ]
[ 620611-27-0 ]

References: [1]Organic and Biomolecular Chemistry,2010,vol. 8,p. 2509 - 2512.

9
[ 147804-30-6 ]
[ 620611-27-0 ]

References: [1]Patent: US2011/256064,2011,A1 .
[2]Patent: WO2014/147636,2014,A1 .
[3]Patent: WO2015/92804,2015,A1 .
[4]Patent: WO2016/128990,2016,A1 .
[5]Patent: EP2377860,2011,A1 .

10
[ 614730-97-1 ]
[ 620611-27-0 ]

References: [1]Patent: US2011/256064,2011,A1 .
[2]Patent: EP2377860,2011,A1 .

11
[ 918431-90-0 ]
[ 620611-27-0 ]

References: [1]Patent: US2011/256064,2011,A1 .
[2]Patent: EP2377860,2011,A1 .

12
4-[(dibenzylamino)methyl]-4-hydroxypiperidine-1-carboxylic acid tert-butyl ester [ No CAS ]
[ 620611-27-0 ]

References: [1]Patent: WO2014/147636,2014,A1 .
[2]Patent: WO2015/92804,2015,A1 .
[3]Patent: WO2016/128990,2016,A1 .

13
tert-butyl 4-[(N,N-dibenzylamino)methyl]-4-fluoropiperidine-1-carboxylate [ No CAS ]
[ 620611-27-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With hydrogen; palladium(II) hydroxide; In methanol; for 8h;	Hydrogen gas was passed into a stirred solution of tert-butyl 4-[(dtbenzylamino)- methyl]-4-fluoro-piperidine- l -carboxylate (4.12 grams, 10 mmole, obtained in the above step) and palladium hydroxide (2 grams, 50 % w/w) in methanol (50 mL) over a period of 8 hours. The progress of the reaction was monitored by thin layer chromatography. After completion of the reaction (thin layer chromatography), the reaction mass was filtered through celite bed and the filtrate was concentrated on rotavaciium to afford the title compound. Yield: 1.97 grams ( 85 %). 'H - NMR (5 ppm): 1.38 (9H, s), 1 .44 - 1 .71 (6H, m), 2.60 - 2.64 (2H, m), 2.95 (2H, bs), 3.73 - 3.76 (2H, m); Mass (m/z): 233.2 (M+H)+.
85%	With hydrogen; palladium(II) hydroxide; In methanol; for 8h;	Hydrogen gas was passed into a stirred solution of tert-Butyl 4-aminomethyl-4-fluoro piperidine- 1 -carboxylate (1.37 grams, 3.28 mmole, obtained in the above step) and palladiumhydroxide (1.37 grams, 50 % w/w) in methanol (30 mL) over a period of 8 hours. The progress of the reaction was monitored by TLC. After completion of the reaction (TLC), the reaction mass was filtered through celite bed and the filtrate was concentrated on rotavacuum to afford the title compound (0.66 gram). Yield: 85 %.?H - NMR (8 ppm): 1.38 (9H, s), 1.44- 1.71 (611, m), 2.60- 2.64 (2H, m), 2.95 (211, bs), 3.73 -3.76 (2H, m).Mass (m/z): 233.2 (M±H).
85%	With hydrogen; palladium(II) hydroxide; In methanol; for 8h;	Hydrogen gas was passed into a stirred solution of tert-butyl 4-[(N,N- dibenzylamino) methyl] -4-fluoro piperidine-l-carboxylate (1.37 grams, 3.28 mmole, obtained in the above step) and palladium hydroxide (1.37 grams, 50 % w/w) in MeOH (30 mL) over a period of 8 hours. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mass was filtered through celite bed and the filtrate was concentrated on rotavacuum to afford the title compound. (0380) Weight: 0.66 grams (Yield: 85 %). (0381) - NMR (delta ppm): 1.38 (9H, s), 1.44 - 1.71 (6H, m), 2.60 - 2.64 (2H, m), 2.95 - 3.04 (2H, m), 3.73 - 3.76 (2H, m); (0382) Mass (m/z): 233.2 (M+H)+.

References: [1]Patent: WO2014/147636,2014,A1 .Location in patent: Page/Page column 33.
[2]Patent: WO2015/92804,2015,A1 .Location in patent: Page/Page column 28.
[3]Patent: WO2016/128990,2016,A1 .Location in patent: Page/Page column 36.

14
[ 620611-27-0 ]
5-amino-6-chloro-N-[4-fluoro-1-(3-methoxy-2,2-dimethylpropyl)-4-piperidinyl]methyl}quinoline-8-carboxamide [ No CAS ]