201150-73-4|tert-Butyl 5-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate| Ambeed

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Quality Control of [ 201150-73-4 ] Purity: 97% SDS Specification

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Product Details of [ 201150-73-4 ]

CAS No. :	201150-73-4
Formula :	C₁₄H₂₀N₂O₂
M.W :	248.32
SMILES Code :	O=C(N1CC2=C(C(N)=CC=C2)CC1)OC(C)(C)C
MDL No. :	MFCD02179750
InChI Key :	SISNTWMRMJDEFB-UHFFFAOYSA-N
Pubchem ID :	17750539

Safety of [ 201150-73-4 ]

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

Computational Chemistry of [ 201150-73-4 ] Show Less

Physicochemical Properties

Num. heavy atoms	18
Num. arom. heavy atoms	6
Fraction Csp3	0.5
Num. rotatable bonds	3
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	76.03
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.	2.65
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	1.96
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.04
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.	1.94
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	1.71
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.06

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.66
Solubility	0.539 mg/ml ; 0.00217 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.75
Solubility	0.44 mg/ml ; 0.00177 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-3.11
Solubility	0.193 mg/ml ; 0.000776 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	Yes
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.	-6.42 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	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.23

Application In Synthesis of [ 201150-73-4 ]

* 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.

Downstream synthetic route of [ 201150-73-4 ]

[ 201150-73-4 ] Synthesis Path-Downstream 1~35

1
[ 115955-90-3 ]
[ 24424-99-5 ]
[ 201150-73-4 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium hydroxide; In 1,4-dioxane; water; at 0 - 20℃;	To a solution of 5-aminotetrahydroisoquinoline (3.68 g, 24.8 mmol) in 1,4-dioxane (100 mL) was added 3 N NaOH (8. 27 mL, 24.8 mmol). After cooling to 0 C, (Boc) 20 (5.42 g, 24.8 mmol) in 1,4-dioxane (10 mL) was added drop-wise and stirred for overnight at room temperature. The reaction mixture was poured into water and extracted with EtOAc (2x). The combined organic layers was washed with sat. aq. NaHC03 solution, water, and brine, then dried and concentrated. The residue was purified by silica gel column chromatography to give 5.44 g (88%) of the desired Boc-protected product as a white solid
2.4 g	With sodium hydroxide; In 1,4-dioxane; water;	334B. tert-Butyl 5-amino-3,4-dihydroisoquinoline-2(lH)-carboxylate: 334A was dissolved in dioxane (20 mL) and 1M NaOH (12.62 mL, 12.62 mmol) and B0C2O was added (2.26 mL, 9.71 mmol). The organic solvent was evaporated and the remaining aqueous was diluted with water (20 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (2 x 20mL) and the combined organic layers were washed with brine (15 mL) and dried (MgS04), and evaporated to give 334B (2.4 g) as a light pink solid. NMR (400MHz, chloroform-d) delta 7.04 (t, J = 7.7 Hz, 1H), 6.70 - 6.52 (m, 2H), 4.57 (s, 2H), 3.76 - 3.72 (m, 2H), 2.59 (t, J = 5.9 Hz, 2H), 1.54 - 1.45 (m, 9H) ppm.

References: [1]Patent: WO2005/37214,2005,A2 .Location in patent: Page/Page column 121-122.
[2]Bioorganic and Medicinal Chemistry,2000,vol. 8,p. 2085 - 2094.
[3]Patent: WO2014/160668,2014,A1 .Location in patent: Page/Page column 357.

2
[ 23053-81-8 ]
[ 201150-73-4 ]
[ 201150-74-5 ]

References: [1]Bioorganic and Medicinal Chemistry,2000,vol. 8,p. 2085 - 2094.

3
[ 1125-60-6 ]
[ 201150-73-4 ]

References: [1]Bioorganic and Medicinal Chemistry,2000,vol. 8,p. 2085 - 2094.
[2]Patent: WO2014/160668,2014,A1 .

4
[ 201150-73-4 ]
N-(1,2,3,4-tetrahydroisoquinolin-5-yl)-5-chloro-2,4-dimethoxybenzamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2000,vol. 8,p. 2085 - 2094.

5
4-chloro-6,7-diethoxyquinoline-3-carboxamide [ No CAS ]
[ 201150-73-4 ]
tert-butyl 5-[3-(aminocarbonyl)-6,7-diethoxyquinolin-4-yl]amino}-3,4-dihydro-(1H)-isoquinoline-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	With acetic acid; In 1-methyl-pyrrolidin-2-one; at 110℃;	Example 251; tert-butyl 5-[3-(aminocarbonyl)-6,7-diethoxyquinolin-4-yl]amino}-3, 4- dihydroisoquinoline-2 ( H)-carboxylate ; A mixture of 4-chloro-6, 7-diethoxyquinoline-3-carboxamide (178 mg, 0.61 mmole, prepared according to WO 02/092571), tert-butyl 5-amino-3,4-dihydroisoquinoline-2 (1H)- carboxylate (198 mg, 0.80 mmole), acetic acid (7 Ill) in NMP (3 ml) was heated over night at 110 C. The reaction mixture was cooled, partitioned between ethyl acetate and sodium hydrogen carbonate solution. The organic layer was washed with water, dried over sodium sulfate and concentrated in vacuum. The residue was purified by flash chromatography eluting with dichloromethane/methanol (10: 0.5) to give the title compound as a light brown powder (214 mg, 69 %). 1H NMR (399.99 MHz, DMSO-d6) 8 10.63 (1H, s), 8.84 (1H, s), 8.24 (1H, br s), 7.58 (1H, br s), 7.22 (1H, s), 7.06 (1H, t), 6.95 (1H, d), 6.65 (2H, s), 6.61 (2H, d), 4.53 (2H, s), 4.15 (2H, q), 3.59 (2H, t), 3.49 (2H, d), 2.70 (2H, t), 1.39 (9H, s), 1.36 (3H, t), 1.06 (3H, t). APCI-LC/MS m/z: 507.2 [MH+]

References: [1]Patent: WO2005/75429,2005,A1 .Location in patent: Page/Page column 94-95.

6
[ 1072084-73-1 ]
[ 201150-73-4 ]
[ 1072084-80-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 80℃; for 3h;	Reference Example 31 5-(4-Chloro-6-morpholin-4-yl-pyrimidin-2-ylamino)-3,4- dihydro-lH-isoquinoline-2-carboxylic acid tert-butyl ester; <n="45"/>A mixture of 4-(6-chloro-2-iodo-pyrimidin-4-yl)-morpholine (326 mg; 1.0 mmol), 5- amino-3,4-dihydro-lH-isoquinoline-2-carboxylic acid tert-buty ester (323 mg; 1.3 mmol), NaOBu' (135 mg; 1.4 mmol), Pd2dba3 (13.7 mg; 0.015 mmol) and Xantphos (28.9 mg; 0.05 mmol) in dioxane (2.5 ml) was stirred under argon at 80 0C for 3 h. The reaction mixture was diluted with water (10 ml) and brine (20 ml) then extracted into CH2Cl2 (2 x 35 ml). The combined organic layers were dried (Na2SO4), concentrated and purified by flash chromatography (60:40 to 70:30 EtO Ac/Petrol) to obtain the title compound as a white solid (114 mg). deltaH (400 MHz, CDCl3) 1.51 (s, 9H), 2.75 (t, J = 6.0, 2H), 3.55-3.58 (m, 4H), 3.69 (t, J = 6.0, 2H), 3.74-3.77 (m, 4H), 4.61 (s, 2H), 6.03 (s, IH), 6.59 (br s, IH), 6.92 (d, J = 8.0, IH), 7.22 (t, J = 8.0, IH), 7.75 (d, J = 8.0, IH).

References: [1]Patent: WO2008/125839,2008,A2 .Location in patent: Page/Page column 42-43.

7
[ 201150-73-4 ]
[ 74-88-4 ]
[ 1051394-64-9 ]

Yield	Reaction Conditions	Operation in experiment
		To <strong>[201150-73-4]tert-butyl 5-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate</strong> (0.26 g, 1.047 mmol) in THF (5 mL), cooled to 0 C , was added NaH (0.105 g, 2.62 mmol). After 15 min, added iodomethane (0.196 mL, 3.14 mmol). After 24 h, additional NaH and iodomethane were added and the reaction was heated to reflux for 4 h. The reaction was quenched with H2O (15 mL) and extracted with EtOAc (3 x 30 mL). The combined organic layers were washed with brine (10 mL) and dried (MgS04). Purification by silica gel chromatography afforded 40A as 0.213 g of a yellow oil. MS (ESI) m/z: 277.1 (M+H)+.
		To a solution of the product from the previous step described above (0.2 g, 0.81 mmol) in THF (5 mL) was added NaH at 0 C. After 15 minutes, CH3I was added and the stirring continued for overnight at room temperature. After completion the reaction mixture was quenched with ice water, extracted with EtOAc (25 mL), dried (Na2S04) and concentrated. The Boc group was removed with 60% TFA-DCM (2 mL) at 0 C to give 110 mg (77.5%) of the final product as a light greenish solid. MS: 177.1 (MH+).

References: [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 9703 - 9723.
[2]Patent: WO2013/56034,2013,A1 .Location in patent: Paragraph 00277.
[3]Patent: WO2005/37214,2005,A2 .Location in patent: Page/Page column 121-122.

8
[ 201150-73-4 ]
[ 1157922-06-9 ]

References: [1]Patent: WO2013/56034,2013,A1 .
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 9703 - 9723.

9
[ 201150-73-4 ]
[ 1430563-70-4 ]

References: [1]Patent: WO2013/56034,2013,A1 .
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 9703 - 9723.

10
[ 79-22-1 ]
[ 201150-73-4 ]
C₁₂H₁₄N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In dichloromethane; for 0.0833333h;	To a separatory funnel was added <strong>[201150-73-4]tert-butyl 5-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate</strong> (0.2 g, 0.805 mmol) in DCM (15 mL) and 1N NaOH (5 mL) , then methyl chloroformate (0.062 mL, 0.805 mmol). The reaction was shaken 5 min and the layers were separated. The organic layer was washed with brine and dried (MgSO4). MS (ESI) m/z: 251 (M+H- tbutyl)+. The compound was heated in 10 mL H2O to 150 C in a microwave for 35 min. Removal of the H2O afforded 0.163 g of 35A as a yellow solid. MS (ESI) m/z: 207 (M+H)+

References: [1]Patent: WO2013/56034,2013,A1 .Location in patent: Paragraph 00272.

11
6-(2-chlorophenyl)-8-methyl-2-(methylsulfinyl)pyrido[2,3-d]-pyrimidin-7(8H)-one [ No CAS ]
[ 201150-73-4 ]
tert-butyl 5-(6-(2-chlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	at 140℃; for 0.5h;	Example 34 Synthesis of 2-(5-(6-(2-chlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]-pyrimidin-2-ylamino)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)-3-cyclopropylacrylonitrile Step 1. A solution of 6-(2-chlorophenyl)-8-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one (0.2 g) and <strong>[201150-73-4]tert-butyl 5-amino-3,4-dihydroisoquinoline-2(1H)-carboxylate</strong> (0.2 g) in DCM (5 mL) was concentrated to remove DCM. The resulted mixture was then stirred at 140 C. for 0.5 h. LCMS showed completion of reaction and the mixture was purified by preparative TLC to afford tert-butyl 5-(6-(2-chlorophenyl)-8-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-ylamino)-3,4-dihydroisoquinoline-2(1H)-carboxylate (150 mg, 48% in yield).

References: [1]Patent: US2014/323464,2014,A1 .Location in patent: Paragraph 0482-0484.

12
[ 201150-73-4 ]
N-(3,4-dihydroisoquinolin-5-yl)-2,2,2-trifluoroacetamide [ No CAS ]

References: [1]Patent: WO2014/160668,2014,A1 .

13
[ 201150-73-4 ]
tert-butyl 4-(2-(1-(3-chloro-2-fluorophenyl)-1H-1,2,3-triazole-4-carbonyl)-5-(2,2,2-trifluoroacetamido)-1,2,3,4-tetrahydroisoquinoline-1-carboxamido)benzoate [ No CAS ]

References: [1]Patent: WO2014/160668,2014,A1 .

14
[ 201150-73-4 ]
tert-butyl 4-(5-amino-2-(1-(3-chloro-2-fluorophenyl)-1H-1,2,3-triazole-4-carbonyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamido)benzoate [ No CAS ]

References: [1]Patent: WO2014/160668,2014,A1 .

15
[ 201150-73-4 ]
4-(5-amino-2-(1-(3-chloro-2-fluorophenyl)-1H-1,2,3-triazole-4-carbonyl)-1,2,3,4-tetrahydroisoquinoline-1-carboxamido)benzoic acid trifluoroacetate [ No CAS ]

References: [1]Patent: WO2014/160668,2014,A1 .

16
[ 407-25-0 ]
[ 201150-73-4 ]
tert-butyl 5-(2,2,2-trifluoroacetamido)-3,4-dihydroisoquinoline-2(1H)-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.27 g	With triethylamine; In dichloromethane; at 0℃;	334C. tert-Butyl 5-(2,2,2-trifluoroacetamido)-3,4-dihydroisoquinoline-2(lH)- carboxylate: To a 0 C solution of 334B (1 g, 4.03 mmol) in DCM (25 mL) was added TEA (0.842 mL, 6.04 mmol) and trifluoroacetic anhydride (0.569 mL, 4.03 mmol). The solvent was evaporated and the residue was purified by normal phase column chromatography to give 334C (1.27 g). XH NMR (400MHz, chloroform-d) delta 7.75 (br. s., 1H), 7.59 (d, J = 6.8 Hz, 1H), 7.34 - 7.25 (m, 1H), 7.10 (d, J = 7.6 Hz, 1H), 4.62 (s, 2H), 3.71 (t, J = 5.9 Hz, 2H), 2.71 (t, J = 5.8 Hz, 2H), 1.51 (s, 9H) ppm. MS (ESI) m/z: 244.9 (M+H-Boc)+.

References: [1]Patent: WO2014/160668,2014,A1 .Location in patent: Page/Page column 357.

17
[ 201150-73-4 ]
5-(carboxymethylamino)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester [ No CAS ]