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Chemical Structure| 1422144-42-0
Chemical Structure| 1422144-42-0
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Product Details of [ 1422144-42-0 ]

CAS No. :1422144-42-0 MDL No. :MFCD29472224
Formula : C30H35N3O9S2 Boiling Point : -
Linear Structure Formula :- InChI Key :QQDRLKRHJOAQDC-FBHGDYMESA-N
M.W : 645.74 Pubchem ID :90410375
Synonyms :
Netarsudil dimesylate;AR-13324 dimesylate

Calculated chemistry of [ 1422144-42-0 ]

Physicochemical Properties

Num. heavy atoms : 44
Num. arom. heavy atoms : 22
Fraction Csp3 : 0.23
Num. rotatable bonds : 9
Num. H-bond acceptors : 11.0
Num. H-bond donors : 4.0
Molar Refractivity : 168.67
TPSA : 219.81 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -9.86 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.99
Log Po/w (XLOGP3) : 0.54
Log Po/w (WLOGP) : 5.72
Log Po/w (MLOGP) : 1.69
Log Po/w (SILICOS-IT) : 5.34
Consensus Log Po/w : 2.85

Druglikeness

Lipinski : 2.0
Ghose : None
Veber : 1.0
Egan : 1.0
Muegge : 3.0
Bioavailability Score : 0.17

Water Solubility

Log S (ESOL) : -3.96
Solubility : 0.0708 mg/ml ; 0.00011 mol/l
Class : Soluble
Log S (Ali) : -4.73
Solubility : 0.0121 mg/ml ; 0.0000187 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -9.57
Solubility : 0.000000174 mg/ml ; 0.0000000003 mol/l
Class : Poorly soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 2.0
Synthetic accessibility : 4.26

Safety of [ 1422144-42-0 ]

Signal Word:Warning Class:
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:
Hazard Statements:H302-H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1422144-42-0 ]

* 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 [ 1422144-42-0 ]

[ 1422144-42-0 ] Synthesis Path-Downstream   1~23

  • 1
  • [ 2097334-19-3 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: water; lithium hydroxide monohydrate; dihydrogen peroxide / tetrahydrofuran / -5 °C 2: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / N,N-dimethyl-formamide / 1 h / 0 - 10 °C 3: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 3 steps 1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / -5 °C 2: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / 2,4,6-trimethyl-pyridine; N,N-dimethyl-formamide / 1 h 3: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 3 steps 1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 2: 2,2,2-trichloro-1,1-dimethylethoxychloroformate; 2,4,6-trimethyl-pyridine / N,N-dimethyl-formamide / 2 h / 0 °C / Inert atmosphere 3: dichloromethane / 22 h / 20 °C / Inert atmosphere
Multi-step reaction with 3 steps 1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 2: pyridine; dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / 24 h / 0 °C / Inert atmosphere 3: dichloromethane / 22 h / 20 °C / Inert atmosphere

  • 2
  • [ 23687-26-5 ]
  • (S)-3-((tert-butoxycarbonyl)amino)-2-(4-(((2,4-dimethylbenzoyl)oxy)methyl)phenyl)propanoic acid [ No CAS ]
  • (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimethanesulfonate [ No CAS ]
  • 3
  • [ 75-75-2 ]
  • [ 1253955-19-9 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
93% In dichloromethane at 20℃; for 22h; Inert atmosphere; (S)-4-[3-Amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]benzyl 2,4-Dimethylbenzoate Dimesylate (10) To (S)-4-{3-[(tert-butoxycarbonyl)amino]-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl}benzyl 2,4-dimethylbenzoate (9) (1.0 g, 1.81 mmol, 99.7 % ee) in CH2Cl2 (8.1 mL) was added methanesulfonic acid (293 μL, 4.52 mL) and the solution was stirred for 22 h at room temperature. The solvents were evaporated and the residue was recrystallized with isopropanol to give pure (S)-4-[3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl]benzyl 2,4-dimethylbenzoate dimesylate (10) (1.1 g, 93%, >99% ee, Chiralpak AS-H) as a off-white crystalline solid. Mp 122-135 °C; [α]D -175 (c 1.0, H2O). IR (ATR): 1708, 1645, 1613, 1563 cm-1. 1H NMR (500 MHz, MeOD): δ = 9.49 (s, 1H), 8.73 (s, 1H), 8.39 (d, J = 6.7 Hz, 1H), 8.34 (d, J = 9.1Hz, 1H), 8.21 (d, J = 6.7 Hz, 1H), 8.00 (dd, J = 3.0, 9.0 Hz, 1H), 7.73 (d, J = 8.1Hz, 1H), 7.53 (dd, J = 8.4, 14.9 Hz, 4 H), 7.03 (s, 1H), 6.99 (d, J = 8.1Hz, 1H), 4.89 (s, 2 H), 4.35 (dd, J = 5.5, 8.7 Hz, 1H), 3.70 (dd, J = 8.9, 12.8 Hz, 1H), 3.34 (dd, J = 5.4, 12.9 Hz, 1H), 2.79 (s, 6 H), 2.46 (s, 3 H), 2.28 (s, 3 H). 13C NMR (125 MHz, MeOD): δ = 172.2, 168.6, 147.5, 146.7, 144.2, 141.9, 141.4, 138.6, 136.5, 133.4, 132.9, 132.4, 131.8, 130.3, 129.6, 127.55, 127.53, 127.46, 125.5, 125.3, 114.9, 66.8, 51.5, 42.8, 39.6, 21.9, 21.3. LC-MS (ES+): m/z = 454 [M + 1 (- 2 CH4O3S)]+, 476 [M + 23 (- 2 CH4O3S)]+. Anal Calcd for C28H27N3O3.2CH4O3S·H2O: C, 54.29; H, 5.62; N, 6.33; S, 9.66. Found: C, 54.04; H, 5.57; N, 6.21; S, 9.77.
90.3% In dichloromethane at 20℃; for 50h; Reflux; 7 (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4- dimethylbenzoate dimethanesulfonate (1): A solution of 3 (242.68 g assay-corrected, 1.0 equiv.) in dichloromethane was treated with methanesulfonic acid (2.5 equiv.) and allowed to stir for 48 h at room temperature. The reaction mixture was then heated to reflux for 2 h. Completion of the reaction was ascertained by TLC assay. A gradual solvent switch from dichloromethane to isopropanol was then carried out. The bulk of the dichloromethane solvent was removed by distillation at 45°C under low vacuum (200-400 mm Hg). Addition of isopropanol, followed by low vacuum distilling at 60°C until 10 volumes of distillate had been collected led to the removal of residual dichloromethane. A second portion of IPA was added and the volume adjusted by low vacuum distilling at 60°C to the initial volume of the reaction mixture. Upon cooling to 20 ± 5°C and stirring for 9 h at this temperature, the dimesylate salt was isolated as a solid by filtration on a 30 micron Teflon filter housed in a filtration reactor under mechanical stirring and a stream of nitrogen. After rinsing with heptane, the resulting pasty solid was transferred to a drying dish and subsequently to a vacuum oven pre-heated at 69°C. After 24.5 h of drying under vacuum, the solid was ground in a glass mortar and pestle. The resulting free flowing solid was submitted for impurity analysis, and the solid met all purity specifications. The solid was further dried under vacuum at 69°C for 96 h to remove residual isopropanol. The solid subsequently met both isopropanol and water content specifications. The title compound was obtained as a white solid (258.7 g; 90.3% assay-corrected yield). 1H NMR (500 MHz, MeOD) δ 2.28 (s, 3 H), 2.46 (s, 3 H), 2.79 (s, 6 H), 3.34 (dd, J= 5.4, 12.9 Hz, 1 H), 3.70 (dd, J= 8.9, 12.8 Hz, 1 H), 4.35 (dd, J= 5.5, 8.7 Hz, 1 H), 4.89 (s, 2 H), 6.99 (d, J= 8.1 Hz, 1 H), 7.03 (s, 1 H), 7.53 (dd, J= 8.4, 14.9 Hz, 4 H), 7.73 (d, J= 8.1 Hz, 1 H), 8.00 (dd, J= 3.0, 9.0 Hz, 1 H), 8.21 (d, J= 6.7 Hz, 1 H), 8.34 (d, J= 9.1 Hz, 1 H), 8.39 (d, J= 6.7 Hz, 1 H), 8.73 (s, 1 H), 9.49 (s, 1 H). 13C NMR (125 MHz, MeOD) δ 21.3, 21.9, 39.6, 42.8, 51.5, 66.8, 114.9, 125.3, 125.4, 125.7, 127.5, 129.6, 130.3, 131.7, 131.8, 132.4, 132.9, 133.4, 136.5, 138.6, 141.4, 141.9, 144.2, 146.7, 147.5, 168.6, 172.2. Chiral LC (>99% ee, Chiralpak AS-H). LC-MS (ES+): m/z = 454 (M+l), 476 (M+23). 1H NMR (500 MHz, d6-DMSO) δ 2.28 (s, 3 H), 2.38 (s, 6 H), 2.46 (s, 3 H), 3.13 (0293) (m, 1 H), 3.59 (m, 1 H), 4.24 (dd, J= 5.2, 8.9 Hz, 1 H), 5.28 (s, 2 H), 7.08 (d, J= 8.07 Hz, 1 H), 7.11 (s, 1 H), 7.48 (s, 4 H), 7.74 (d, J= 7.9 Hz, 1 H), 7.99 (m, 4 H), 8.35 (d, J= 6.5 Hz, 1 H), 8.45 (d, J= 9.1 Hz, 1 H), 8.55 (d, J= 6.6 Hz, 1 H), 8.69 (s, 1 H), 9.68 (s, 1 H). 13C NMR (125 MHz, d6-DMSO) δ 20.9, 21.2, 40.7, 49.8, 65.4, 113.3, 123.5, 123.8, 123.9, 126.1, 126.6, 126.7, 128.1, 128.6, 130.4, 131.8, 132.2, 132.4, 135.8, 136.2, 139.6, 142.5, 145.2, 146.1, 166.4, 170.5. Chiral LC (>99% ee, Chiralpak AS-H). LC-MS (ES+): m/z = 454 (M+l), 476 (M+23).
90.3% In dichloromethane at 20℃; for 50h; Reflux; 7 : (S)-4-(3-Amino-1 -(isoquinolin-6-ylamino)-1 -oxopropan-2-yl)benzyl 2,4-dimethylben- zoate dimethanesulfonate (1) A solution of 3 (242.68 g assay-corrected, 1.0 equiv.) indichloromethane was treated with methanesulfonic acid (2.5 equiv.) and allowed to stir for 48 h at room temperature. The reaction mixture was then heated to reflux for 2 h. Completion of the reaction was ascertained by TLC assay. A gradual solvent switch from dichloromethane to isopropanol wasthen carried out. The bulk of the dichloromethane solvent was removed by distillation at 45° C. under low vacuum (200-400mm Hg). Addition of isopropanol, followed by low (s, 3H), 2.46 (s, 3H), 2.79 (s, 6H), 3.34 (dd, J=5.4, 12.9 Hz, 1H), 3.70 (dd, J=8.9, 12.8 Hz, 1H), 4.35 (dd, J=5.5, 8.7 Hz, 1H), 4.89 (s, 2H), 6.99 (d, J=8.1 Hz, 1H), 7.03 (s, 1H), 7.53 (dd, J=8.4, 14.9 Hz, 4H), 7.73 (d, J=8.1 Hz, 1H), 8.00 (dd, J=3.0, 9.0 Hz, 1H), 8.21 (d, J=6.7 Hz, 1H), 8.34 (d, J=9.1 Hz, 1H), 8.39 (d, J=6.7 Hz, 1H), 8.73 (s, 1H), 9.49 (s, 1H). 13CNMR (125 MHz, MeOD) ö 21.3, 21.9, 39.6, 42.8, 51.5,66.8, 114.9, 125.3, 125.4, 125.7, 127.5, 129.6, 130.3, 131.7,131.8, 132.4, 132.9, 133.4, 136.5, 138.6, 141.4, 141.9,144.2, 146.7, 147.5, 168.6, 172.2. Chiral LC (>99% cc, Chiralpak AS-H). LC-MS (ES+): mlz=454 (M+i), 476 (M+23).‘H NMR (500 MHz, d5-DMSO) ö 2.28 (s, 3H), 2.38 (s,6H), 2.46 (s, 3H), 3.13 (m, 1H), 3.59 (m, 1H), 4.24 (dd,J=5.2, 8.9 Hz, 1H), 5.28 (s, 2H), 7.08 (d, J=8.07 Hz, 1H),7.11 (s, 1H), 7.48 (s, 4H), 7.74 (d, J=7.9 Hz, 1H), 7.99 (m,4H), 8.35 (d, J=6.5 Hz, 1H), 8.45 (d, J=9.i Hz, 1H), 8.55 (d,J=6.6 Hz, 1H), 8.69 (s, 1H), 9.68 (s, 1H). 13C NMR (125MHz, d6-DMSO) ö 20.9, 21.2, 40.7, 49.8, 65.4, 113.3,123.5, 123.8, 123.9, 126.1, 126.6, 126.7, 128.1, 128.6,130.4, 131.8, 132.2, 132.4, 135.8, 136.2, 139.6, 142.5,145.2, 146.1, 166.4, 170.5. Chiral LC (>99% cc, ChiralpakAS-H). LC-MS (ES+): m/z=454 (M+i), 476 (M+23).**diHCl salt: ‘H NMR (300 MHz, MeOD) ö 2.25 (s,3H), 2.43 (s, 3H), 3.05 (m, 1H), 3.4 (m, 1H), 3.98 (dd, J=5.7,8.4 Hz, 1H), 5.23 (s, 2H), 6.94 (d, J=7.9 Hz, 1H), 6.98 (s,1H), 7.42 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.4 Hz, 2H), 7.58 (d,J=6.0 Hz, 1H), 7.64 (dd, J=2.i, 9.0 Hz, 1H), 7.70 (d, J=8.iHz, 1H), 7.88 (d, J=9.0 Hz, 1H), 8.25 (d, J=6.0 Hz, 1H), 8.31(s, 1H), 8.98 (s, 1H). 13C NMR (75 MHz, MeOD) ö 21.3,21.9, 45.3, 55.7, 66.9, 115.3, 122.1, 122.7, 127.0, 127.5,129.4, 129.8, 129.9, 129.9, 131.8, 133.4, 137.6, 138.4,138.7, 141.4, 142.2, 143.0, 144.1, 152.3, 168.6, 173.1.Chiral LC (>95% cc, Chiralpak AS-H); LC-MS (ES+):mlz=454 (M+i).**free base: ‘H NMR (500 MHz, MeOD) ö 2.25 (s, 3H),2.44 (s, 3H), 2.98 (dd, J=5.7, 12.9 Hz, 1H), 3.35 (dd, J=8.7,12.8 Hz, 1H), 3.87 (dd, J=5.7, 8.6 Hz, 1H), 5.23 (s, 2H), 6.94(d, J=7.9 Hz, 1H), 6.98 (s, 1H), 7.42 (d, J=8.2 Hz, 2H), 7.45(d, J=8.2 Hz, 2H), 7.59 (d, J=5.9 Hz, 1H), 7.63 (d, 8.9 Hz,1H), 7.71 (d, J=7.9 Hz, 1H), 7.89 (d, J=9.i Hz, 1H), 8.25 (d,J=5.9 Hz, 1H), 8.3 (s, 1H), 8.9 (s, 1H). 13C NMR (125 MHz,MeOD) ö 21.3, 21.9, 45.9, 56.8, 66.9, 115.2, 122.0, 122.7,126.9, 127.5, 127.6, 129.3, 129.8, 129.8, 131.8, 133.4,137.3, 138.4, 139.2, 141.4, 142.2, 143.0, 144.1, 152.3,168.6, 173.5.
85% In dichloromethane at 20 - 35℃; for 27h; Inert atmosphere; 1 Synthesis of compound netadil dimethanesulfonate Dissolve compound 10 (2.5g, 4.52mmol) in 25ml of dichloromethane, add methanesulfonic acid (1.1g, 110.3mmol) under nitrogen protection, stir at room temperature for 24 hours, and then warm to 35 °C for 3 hours. TLC monitors the completion of the raw material reaction. Rotate the dichloromethane to obtain a light yellow oil, and then use isopropanol to dry the residual dichloromethane to obtain a white solid. Under the protection of nitrogen, the white solid was recrystallized with 30 ml of isopropanol, and filtered under the protection of nitrogen. The filter cake was slurried with n-heptane and dried under vacuum, then slurried with isopropanol, and dried under vacuum. The filter cake was dried in vacuum at 65°C±5°C for 24 hours to obtain the pure compound netadil dimethanesulfonate (2.3g) with a yield of 85%, a purity of 99%, and an optical purity of 99%.
2.52 g In dichloromethane at 20℃; for 15h; 10 Example 10
Preparation of Netarsudil Mesylate Form N3
To a stirred solution of (S)-4-(3-((tert-butoxycarbonyl)amino)-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate (5.0 g 1 eq.) in DCM (dichloromethane) (10 vol), methanesulfonic acid (2.5 eq) was added dropwise. The reaction mixture was stirred at room temperature over 15 h and completion of the reaction was ascertained by HPLC. A gradual solvent switch from DCM to 2-BuOH was then carried out. The solution of the DCM solvent was removed by distillation under vacuum. Next, two substantial portions of 2-BuOH were added to the residue follows by vacuum distillation. Eventually, 2-BuOH (10 vol) was added to the residue and the reaction mixture was stirred at room temperature over a period of 15 h. The dimesylate salt was isolated as a solid by filtration under nitrogen. After washing with 2-BuOH (2*1 vol) and heptane (2*1 vol), the solid was dried upon vacuum oven at 40° C. over 15 h. The compound was obtained as a white solid (2.52 g). Netarsudil mesylate form N3 has been confirmed by XRPD.

  • 4
  • [ 622-47-9 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 11 steps 1.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / acetonitrile / 80 °C / Large scale 2.1: sodium hydroxide / water / 18 - 25 °C / Large scale 3.1: sulfuric acid / 0 - 25 °C / Large scale 4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 1 h / 18 - 25 °C / Large scale 4.2: 18 - 25 °C / Large scale 5.1: lithium hydroxide; water / tetrahydrofuran / 2.5 h / Large scale 6.1: oxalyl dichloride / dichloromethane / 18 h / 18 - 25 °C 7.1: n-butyllithium / tetrahydrofuran; n-heptane / 0.5 h / -70 - -65 °C 8.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 8.2: 1.5 h / -30 °C 9.1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / -5 °C 10.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / 2,4,6-trimethyl-pyridine; N,N-dimethyl-formamide / 1 h 11.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 11 steps 1.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / acetonitrile / 80 °C / Large scale 2.1: sodium hydroxide / water / 20 °C / Large scale 3.1: sulfuric acid / 0 - 20 °C / Large scale 4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 1 h / 20 °C / Large scale 4.2: 20 °C / Large scale 5.1: water; lithium hydroxide / tetrahydrofuran / 2.5 h / Large scale 6.1: oxalyl dichloride / dichloromethane / 18 h / 20 °C 7.1: n-butyllithium / tetrahydrofuran; n-heptane / 0.5 h / -70 - -65 °C 8.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 8.2: 1.5 h / -30 °C 9.1: water; lithium hydroxide monohydrate; dihydrogen peroxide / tetrahydrofuran / -5 °C 10.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / N,N-dimethyl-formamide / 1 h / 0 - 10 °C 11.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 11 steps 1.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / acetonitrile / 0.5 h / 80 °C 2.1: sodium hydroxide; water / 24 h / 20 °C 3.1: 1H-imidazole / N,N-dimethyl-formamide / 0 - 20 °C 4.1: oxalyl dichloride / tetrahydrofuran / 0 °C 5.1: n-butyllithium / tetrahydrofuran / 1 h / -70 - -65 °C / Inert atmosphere 5.2: 2 h / -70 - -65 °C / Inert atmosphere 6.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 - -65 °C / Inert atmosphere 6.2: 3 h / -30 - -25 °C / Inert atmosphere 7.1: water; dihydrogen peroxide; lithium hydroxide / tetrahydrofuran / -5 - 0 °C 8.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / dichloromethane / 20 °C / Inert atmosphere 9.1: tetrabutyl ammonium fluoride / tetrahydrofuran 10.1: triethylamine / dichloromethane / 0 - 5 °C / Inert atmosphere 11.1: dichloromethane / 27 h / 20 - 35 °C / Inert atmosphere
  • 5
  • [ 2097334-16-0 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: oxalyl dichloride / dichloromethane / 18 h / 20 °C 2.1: n-butyllithium / tetrahydrofuran; n-heptane / 0.5 h / -70 - -65 °C 3.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 3.2: 1.5 h / -30 °C 4.1: water; lithium hydroxide monohydrate; dihydrogen peroxide / tetrahydrofuran / -5 °C 5.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / N,N-dimethyl-formamide / 1 h / 0 - 10 °C 6.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 6 steps 1.1: oxalyl dichloride / dichloromethane / 18 h / 18 - 25 °C 2.1: n-butyllithium / tetrahydrofuran; n-heptane / 0.5 h / -70 - -65 °C 3.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 3.2: 1.5 h / -30 °C 4.1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / -5 °C 5.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / 2,4,6-trimethyl-pyridine; N,N-dimethyl-formamide / 1 h 6.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 6 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / tetrahydrofuran / 1.25 h / 0 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 2.2: 1 h / -78 °C / Inert atmosphere 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Acidic conditions 3.2: -78 - -25 °C / Inert atmosphere 4.1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 5.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate; 2,4,6-trimethyl-pyridine / N,N-dimethyl-formamide / 2 h / 0 °C / Inert atmosphere 6.1: dichloromethane / 22 h / 20 °C / Inert atmosphere
Multi-step reaction with 6 steps 1.1: oxalyl dichloride; N,N-dimethyl-formamide / tetrahydrofuran / 1.25 h / 0 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 2.2: 1 h / -78 °C / Inert atmosphere 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Acidic conditions 3.2: -78 - -25 °C / Inert atmosphere 4.1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 5.1: pyridine; dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / 24 h / 0 °C / Inert atmosphere 6.1: dichloromethane / 22 h / 20 °C / Inert atmosphere

  • 6
  • [ 13737-36-5 ]
  • (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimethanesulfonate [ No CAS ]
  • 7
  • [ 73401-74-8 ]
  • (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimethanesulfonate [ No CAS ]
  • 8
  • [ 155380-11-3 ]
  • (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimethanesulfonate [ No CAS ]
  • 9
  • [ 2097334-15-9 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: water; lithium hydroxide / tetrahydrofuran / 2.5 h / Large scale 2.1: oxalyl dichloride / dichloromethane / 18 h / 20 °C 3.1: n-butyllithium / tetrahydrofuran; n-heptane / 0.5 h / -70 - -65 °C 4.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 4.2: 1.5 h / -30 °C 5.1: water; lithium hydroxide monohydrate; dihydrogen peroxide / tetrahydrofuran / -5 °C 6.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / N,N-dimethyl-formamide / 1 h / 0 - 10 °C 7.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 7 steps 1.1: lithium hydroxide; water / tetrahydrofuran / 2.5 h / Large scale 2.1: oxalyl dichloride / dichloromethane / 18 h / 18 - 25 °C 3.1: n-butyllithium / tetrahydrofuran; n-heptane / 0.5 h / -70 - -65 °C 4.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 4.2: 1.5 h / -30 °C 5.1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / -5 °C 6.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / 2,4,6-trimethyl-pyridine; N,N-dimethyl-formamide / 1 h 7.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 7 steps 1.1: lithium hydroxide monohydrate / water; acetonitrile; 1,4-dioxane / 0.67 h / 0 - 20 °C / Inert atmosphere 2.1: oxalyl dichloride; N,N-dimethyl-formamide / tetrahydrofuran / 1.25 h / 0 °C / Inert atmosphere 3.1: n-butyllithium / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 3.2: 1 h / -78 °C / Inert atmosphere 4.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Acidic conditions 4.2: -78 - -25 °C / Inert atmosphere 5.1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 6.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate; 2,4,6-trimethyl-pyridine / N,N-dimethyl-formamide / 2 h / 0 °C / Inert atmosphere 7.1: dichloromethane / 22 h / 20 °C / Inert atmosphere
Multi-step reaction with 7 steps 1.1: lithium hydroxide monohydrate / water; acetonitrile; 1,4-dioxane / 0.67 h / 0 - 20 °C / Inert atmosphere 2.1: oxalyl dichloride; N,N-dimethyl-formamide / tetrahydrofuran / 1.25 h / 0 °C / Inert atmosphere 3.1: n-butyllithium / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 3.2: 1 h / -78 °C / Inert atmosphere 4.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Acidic conditions 4.2: -78 - -25 °C / Inert atmosphere 5.1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 6.1: pyridine; dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / 24 h / 0 °C / Inert atmosphere 7.1: dichloromethane / 22 h / 20 °C / Inert atmosphere

  • 10
  • [ 2097334-17-1 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran; n-heptane / 0.5 h / -70 - -65 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 2.2: 1.5 h / -30 °C 3.1: water; lithium hydroxide monohydrate; dihydrogen peroxide / tetrahydrofuran / -5 °C 4.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / N,N-dimethyl-formamide / 1 h / 0 - 10 °C 5.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran; n-heptane / 0.5 h / -70 - -65 °C 2.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 2.2: 1.5 h / -30 °C 3.1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / -5 °C 4.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / 2,4,6-trimethyl-pyridine; N,N-dimethyl-formamide / 1 h 5.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 1.2: 1 h / -78 °C / Inert atmosphere 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Acidic conditions 2.2: -78 - -25 °C / Inert atmosphere 3.1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 4.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate; 2,4,6-trimethyl-pyridine / N,N-dimethyl-formamide / 2 h / 0 °C / Inert atmosphere 5.1: dichloromethane / 22 h / 20 °C / Inert atmosphere
Multi-step reaction with 5 steps 1.1: n-butyllithium / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 1.2: 1 h / -78 °C / Inert atmosphere 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Acidic conditions 2.2: -78 - -25 °C / Inert atmosphere 3.1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 4.1: pyridine; dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / 24 h / 0 °C / Inert atmosphere 5.1: dichloromethane / 22 h / 20 °C / Inert atmosphere

  • 11
  • [ CAS Unavailable ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 1.2: 1.5 h / -30 °C 2.1: water; lithium hydroxide monohydrate; dihydrogen peroxide / tetrahydrofuran / -5 °C 3.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / N,N-dimethyl-formamide / 1 h / 0 - 10 °C 4.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 4 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran; n-heptane / 0.67 h / -70 - -65 °C 1.2: 1.5 h / -30 °C 2.1: dihydrogen peroxide; lithium hydroxide monohydrate / water; tetrahydrofuran / -5 °C 3.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / 2,4,6-trimethyl-pyridine; N,N-dimethyl-formamide / 1 h 4.1: dichloromethane / 50 h / 20 °C / Reflux
Multi-step reaction with 4 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Acidic conditions 1.2: -78 - -25 °C / Inert atmosphere 2.1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 3.1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate; 2,4,6-trimethyl-pyridine / N,N-dimethyl-formamide / 2 h / 0 °C / Inert atmosphere 4.1: dichloromethane / 22 h / 20 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -78 °C / Acidic conditions 1.2: -78 - -25 °C / Inert atmosphere 2.1: lithium hydroxide monohydrate; dihydrogen peroxide / water; tetrahydrofuran / 0.75 h / 0 °C / Inert atmosphere 3.1: pyridine; dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / 24 h / 0 °C / Inert atmosphere 4.1: dichloromethane / 22 h / 20 °C / Inert atmosphere

  • 12
  • [ 2097334-20-6 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: 2,2,2-trichloro-1,1-dimethylethoxychloroformate / 2,4,6-trimethyl-pyridine; N,N-dimethyl-formamide / 1 h 2: dichloromethane / 50 h / 20 °C / Reflux
  • 13
  • [ 1422144-42-0 ]
  • [ 1253952-02-1 ]
YieldReaction ConditionsOperation in experiment
Stage #1: (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimethanesulfonate With sodium hydrogencarbonate In water for 0.5h; Stage #2: With hydrogenchloride In 1,4-dioxane; dichloromethane Inert atmosphere; 1,2 Example 1. Synthesis of the mono-(hydrochloric acid) salt of (S)-4-(3-amino-1- (isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate Preparation of (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl) benzyl 2,4- dimethylbenzoate·. The dimesylate salt of (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan- 2-yl)benzyl 2,4-dimethylbenzoate (20.5 g, 31.75 mmol) was dissolved in water (80 ml_) and treated with a NaHC03 saturated solution (55 ml_) portion wise over 10 minutes until pH 7.5. The resulting slurry was stirred 20 minutes and then extracted with CH2CI2/EtOH (500 mL/30ml_) and CH2CI2 (4 x 100 ml_). The organic layers were washed with brine (50 ml_), dried over Na2S04 and concentrated to give 15.3 g (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1- oxopropan-2-yl)benzyl 2,4-dimethylbenzoate. The product was dried on a high vacuum overnight at 30 °C. 1H-NMR showed that some solvent was still present in the product which was split on 2 portions: 9 g was moved to the next step and the rest (5.1 g) was dried during 3 days under high vacuum at 40 °C. The latter one provided the first target compound, (S)-4-(3- amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate (5 g). The total yield for this step was 95%. (0190) Preparation of mono-(hydrochloric acid) salt of (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1- oxopropan-2-yi) benzyl 2,4-dimethylbenzoate·. A solution of (S)-4-(3-amino-1-(isoquinolin-6- ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate (9.0 g, 19.84 mmol) in dry CH2CI2 (100 ml_) was treated with 4N HCI in dioxane (1 eq, 4.96 ml_, 19.84 mmol) over 5 minutes under N2 and stirring. The resulting slurry was left to stir overnight. The reaction mixture was concentrated with toluene (2 x 50 ml_) and dried on a high vacuum for 3 days at 40°C to give mono-(hydrochloric acid) salt of (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2- yl)benzyl 2,4-dimethylbenzoate (9.6 g, 97%).
  • 14
  • [ 1422144-42-0 ]
  • [ 1253952-02-1 ]
YieldReaction ConditionsOperation in experiment
Stage #1: (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate dimethanesulfonate With water; sodium hydrogencarbonate In dichloromethane Stage #2: With hydrogenchloride In 1,4-dioxane; dichloromethane for 2h; 3 Example 3. Synthesis of di-(hydrochloric acid) salt of (S)-4-(3-amino-1-(isoquinolin-6- ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate Preparation of di-(hydrochloric acid) salt of (S)-4-(3-amino-1-(isoquinolin-6-ylamino)-1- oxopropan-2-yl) benzyl 2,4-dimethylbenzoate·. A solution of (S)-4-(3-amino-1-(isoquinolin-6- ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate (250 mg, 0.55 mmol) in dry CH2CI2 (3.2 mL) was treated with 4N HCI in dioxane (2.5 eq, 343 pL, 1.38 mmol). After 2 hours the solvents were evaporated and the solids were azeotroped with toluene (3 x 3 mL) and dried on the high vacuum for 4 days at 40 °C to give di-(hydrochloric acid) salt of (S)-4-(3-amino-1-(isoquinolin-6- ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate (268 mg, 93%).
  • 15
  • [ 75-75-2 ]
  • [ 2574473-80-4 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
0.7 g Stage #1: (S)-netarsudil mono(-)-O,O'-di-p-toluoyl-L-tartrate With ammonium hydroxide In dichloromethane at 20 - 30℃; for 0.5h; Stage #2: methanesulfonic acid In isopropyl alcohol at 0 - 10℃; 8 Example 8: Preparation of (S)-Netarsudil dimesylate (S)-Netarsudil (-)-O,O -di-p-toluoyl-L-tartrate salt (1.0 g), and dichloromethane (50 mL) were charged in the flask at 20-30°C. Aqueous ammonia was added & stirred for 30 minutes. The layers were separated and dichloromethane layer was distilled under vacuum at 40-45°C. Isopropanol (20 mL) was charged in the flask at 20-30°C. Methane sulfonic acid (0.27 g dissolved in Isopropanol 10 mL) was then added at 0-10°C and stirred at 0-10°C. The reaction mixture was filtered, washed with chilled Isopropanol (10 mL) and dried the solid under vacuum at 60 °C for 24 hours to obtain the titled compound. Yield: 0.7 g HPLC purity >99% Chiral purity >99% ee
  • 16
  • [ 2674042-89-6 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / dichloromethane / 20 °C / Inert atmosphere 2: tetrabutyl ammonium fluoride / tetrahydrofuran 3: triethylamine / dichloromethane / 0 - 5 °C / Inert atmosphere 4: dichloromethane / 27 h / 20 - 35 °C / Inert atmosphere
  • 17
  • [ 2674042-92-1 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: tetrabutyl ammonium fluoride / tetrahydrofuran 2: triethylamine / dichloromethane / 0 - 5 °C / Inert atmosphere 3: dichloromethane / 27 h / 20 - 35 °C / Inert atmosphere
  • 18
  • [ 2166548-09-8 ]
  • [ 21900-42-5 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 0 - 5 °C / Inert atmosphere 2: dichloromethane / 27 h / 20 - 35 °C / Inert atmosphere
  • 19
  • [ 2753642-03-2 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / -70 - -65 °C / Inert atmosphere 1.2: 2 h / -70 - -65 °C / Inert atmosphere 2.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 - -65 °C / Inert atmosphere 2.2: 3 h / -30 - -25 °C / Inert atmosphere 3.1: water; dihydrogen peroxide; lithium hydroxide / tetrahydrofuran / -5 - 0 °C 4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / dichloromethane / 20 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran 6.1: triethylamine / dichloromethane / 0 - 5 °C / Inert atmosphere 7.1: dichloromethane / 27 h / 20 - 35 °C / Inert atmosphere
  • 20
  • [ 611-01-8 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: oxalyl dichloride / dichloromethane / 5 - 20 °C 2: triethylamine / dichloromethane / 0 - 5 °C / Inert atmosphere 3: dichloromethane / 27 h / 20 - 35 °C / Inert atmosphere
  • 21
  • [ 2753642-02-1 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 8 steps 1.1: oxalyl dichloride / tetrahydrofuran / 0 °C 2.1: n-butyllithium / tetrahydrofuran / 1 h / -70 - -65 °C / Inert atmosphere 2.2: 2 h / -70 - -65 °C / Inert atmosphere 3.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 - -65 °C / Inert atmosphere 3.2: 3 h / -30 - -25 °C / Inert atmosphere 4.1: water; dihydrogen peroxide; lithium hydroxide / tetrahydrofuran / -5 - 0 °C 5.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / dichloromethane / 20 °C / Inert atmosphere 6.1: tetrabutyl ammonium fluoride / tetrahydrofuran 7.1: triethylamine / dichloromethane / 0 - 5 °C / Inert atmosphere 8.1: dichloromethane / 27 h / 20 - 35 °C / Inert atmosphere
  • 22
  • [ 2674042-85-2 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 1 h / -70 - -65 °C / Inert atmosphere 1.2: 3 h / -30 - -25 °C / Inert atmosphere 2.1: water; dihydrogen peroxide; lithium hydroxide / tetrahydrofuran / -5 - 0 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / dichloromethane / 20 °C / Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran 5.1: triethylamine / dichloromethane / 0 - 5 °C / Inert atmosphere 6.1: dichloromethane / 27 h / 20 - 35 °C / Inert atmosphere
  • 23
  • [ 2674042-87-4 ]
  • [ 1422144-42-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1: water; dihydrogen peroxide; lithium hydroxide / tetrahydrofuran / -5 - 0 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol; triethylamine / dichloromethane / 20 °C / Inert atmosphere 3: tetrabutyl ammonium fluoride / tetrahydrofuran 4: triethylamine / dichloromethane / 0 - 5 °C / Inert atmosphere 5: dichloromethane / 27 h / 20 - 35 °C / Inert atmosphere
Same Skeleton Products
Historical Records

Similar Product of
[ 1422144-42-0 ]

Chemical Structure| 1254032-66-0

A946595[ 1254032-66-0 ]

(S)-4-(3-Amino-1-(isoquinolin-6-ylamino)-1-oxopropan-2-yl)benzyl 2,4-dimethylbenzoate

Reason: Free-salt