[ CAS No. 116529-62-5 ] {[proInfo.proName]}

Name: 116529-62-5|4-Iodo-2-nitrobenzoic acid|97%
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SKU: A262273
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Quality Control of [ 116529-62-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 116529-62-5 ]

CAS No. :	116529-62-5	MDL No. :	MFCD09909618
Formula :	C₇H₄INO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	IZBFYNYRKIUGSG-UHFFFAOYSA-N
M.W :	293.02	Pubchem ID :	18919883
Synonyms :

Calculated chemistry of [ 116529-62-5 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	54.94
TPSA :	83.12 Å²

Pharmacokinetics

GI absorption :	High
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) :	-6.59 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.91
Log Po/w (XLOGP3) :	2.11
Log Po/w (WLOGP) :	1.9
Log Po/w (MLOGP) :	1.43
Log Po/w (SILICOS-IT) :	0.07
Consensus Log Po/w :	1.28

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.2
Solubility :	0.187 mg/ml ; 0.000637 mol/l
Class :	Soluble
Log S (Ali) :	-3.49
Solubility :	0.0956 mg/ml ; 0.000326 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.09
Solubility :	2.36 mg/ml ; 0.00805 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	3.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	2.2

Safety of [ 116529-62-5 ]

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

Application In Synthesis of [ 116529-62-5 ]

* 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 [ 116529-62-5 ]
Downstream synthetic route of [ 116529-62-5 ]

[ 116529-62-5 ] Synthesis Path-Upstream 1~2

1
[ 116529-62-5 ]
[ 20776-54-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With tin(ll) chloride In ethyl acetate at 20℃; for 16 h;	B. 2-Amino-4-iodo-benzoic acid. ; 4-lodo-2-nitro-benzoic acid (20 g, 68 mmol, 1.0 equiv.) was dissolved in 200 mL of EtOAc and then SnCl₂.2H₂O (46 g, 204 mmol, 3.0 equiv.) was added in three portions. The reaction mixture was stirred at rt for 16 h. Satd. aq. NaHCO₃was carefully added to adjust the mixture to pH=9. The precipitated solid was removed by filtration through diatomaceous earth, washing with water. The aqueous layer in the filtrate was separated and acidified with conc. HCl to pH=2. The precipitated solid was collected by filtration and dried to afford the title compound as white solid (19 g, 68 mmol, 100percent). ¹H NMR (400 MHz, CD₃OD): ¹H NMR (500 MHz, CDCl₃): 7.56 (d, J=8.5, 1H), 7.08 (s, 1H), 6.99 (d, J=8.5, 1H), 5.71 (br s, 2H).

Reference： [1] Patent: US2006/69286, 2006, A1, . Location in patent: Page/Page column 26
[2] American Chemical Journal, 1910, vol. 44, p. 448

2
[ 116529-62-5 ]
[ 7664-41-7 ]
[ 20776-54-9 ]

Reference： [1] American Chemical Journal, 1910, vol. 44, p. 448

[ 116529-62-5 ] Synthesis Path-Downstream 1~24

1
[ 41252-97-5 ]
[ 116529-62-5 ]

Yield	Reaction Conditions	Operation in experiment
83%		A. 4-lodo-2-nitro-benzoic acid.; In a 1 L three-neck round-bottom flask equipped with an internal thermometer, a reflux condenser, and an addition funnel, Bu4N+MnO4- (124 g, 343 mmol) was dissolved in pyridine (200 mL). The solution was heated to 60 C., and then the heating source was removed. A solution of <strong>[41252-97-5]4-iodo-2-nitrotoluene</strong> (43.0 g, 163 mmol) in pyridine (60 mL) was added through the additional funnel over2 h. The reaction temperature was maintained at 60 C. by adjusting the addition rate. When the addition was complete, the reaction mixture was cooled to rt. The solution was concentrated, diluted with EtOAc (300 mL) and water (200 mL), and stirred at rt for 30 min. The precipitated brown solid was filtered off and washed with EtOAc. The clear organic layer was washed with 5% aq. H2SO4 (200 mL) and brine (200 mL), dried (MgSO4), and concentrated to afford a thick, brown oil. The crude product was dissolved in EtOAc (200 mL) and then a solution of KOH (9.1 g, 163 mmol) in MeOH (ca. 30 mL) was added dropwise. The mixture was stirred at rt for 1 h, and the precipitated solid was collected by filtration and washed with EtOAc. The filtrate was concentrated and the precipitation was repeated with KOH in MeOH. The two crops were combined and dissolved in water (ca. 250 mL) and acidified with conc. HCl to pH<2. The precipitated white solid was collected by filtration and dried under vacuum to give the desired product (40 g, 136 mmol, 83%, >98% purity by HPLC). 1H NMR (400 MHz, CD3OD): 8.13 (d, J=1.6, 1H), 8.01 (dd, J=8.1, 1.6, 1H), 7.50 (d, J=8.1, 1H).
22%		Example 1: Synthesis of compounds of formula i; 2-Amino-4-methoxy-benzoic acid methyl ester; Step 1 : 4-Iodo-2-nitrobenzoic acid; To a mixture of <strong>[41252-97-5]4-iodo-2-nitrotoluene</strong> (9.0 g, 34 mmol) in H2O (340 mL) was added KMnO4 (22.0 g, 139 mmol). The mixture was heated at reflux for 5 h and then cooled to rt and filtered through Celite. The filtrate was acidified to pH=2 with cone. HCl. The precipitate that formed and was filtered and dried to give 4-iodo-2-nitrobenzoic acid (2.0 g, 20%). The filtrate was extracted with DCM (3 x 200 mL). The organic solutions were combined, dried over Na2SO4, filtered, and concentrated to provide a second lot of 4-iodo-2-nitrobenzoic acid (0.18 g, 2%).
20%	With potassium permanganate; In water; for 5h;Heating / reflux;	A. 4-Iodo-2-nitrobenzoic acid 4-Iodo-2-nitrotoluene (9.0 g, 34.2 mmol), KMnO4 (22.0 g, 139 mmol) and water (340 mL) were heated at reflux for 5 h. The resulting brown suspension of MnO2 was filtered off through a pad of diatomaceous earth, and the filter cake was washed with water. The basic filtrate was acidified with concentrated HCl causing crystallization of the desired acid. The crystals were collected by suction filtration and dried affording 1.86 g of the acid. The mother liquor was extracted with DCM (3*200 mL), and the combined extracts were dried (Na2SO4) and concentrated in vacuo to afford an additional 0.16 g of the benzoic acid. Total yield=2.02 g (20%). 1H NMR (400 MHz, CD3OD): 8.13 (d, J=1.6 Hz, 1H), 8.01 (dd, J=8.1, 1.6 Hz, 1H), 7.50 (d, J=8.1 Hz, 1H).

20%		A. 4-Iodo-2-nitrobenzoic acid. 4-Iodo-2-nitrotoluene (9.0 g, 34 mmol), KMnO4 (22.0 g, 139 mmol), and H2O (340 mL) were heated at reflux for 5 h. The resulting brown suspension was filtered through a pad of diatomaceous earth, and the filter cake was washed with H2O. The basic filtrate was acidified with concentrated HCl causing precipitation of the desired acid. The solid was collected by suction filtration and dried, affording 1.86 g of the acid. The mother liquor was extracted with DCM (3*200 mL), and the combined extracts were dried (Na2SO4) and concentrated in vacuo to afford an additional 0.16 g of the benzoic acid (total 2.02 g, 20%). 1H NMR (400 MHz, CD3OD): 8.13 (d, J=1.6 Hz, 1H), 8.01 (dd, J=8.1, 1.6 Hz, 1H), 7.50 (d, J=8.1 Hz, 1H).
20%		A. 4-Iodo-2-nitrobenzoic acid. ; 4-Iodo-2-nitrotoluene (9.0 g, 34.2 mmol), KMnO4(22.0 g, 139 mmol) and water (340 mL) were heated at reflux for 5 h. The resulting brown suspension was filtered through a pad of diatomaceous earth, washing with water. The basic filtrate was acidified with conc. HCl. The resulting solids were collected by suction filtration and dried to afford 1.86 g of the acid. The mother liquor was extracted with DCM (3×), and the combined extracts were dried (Na2SO4) and concentrated to afford an additional 0.16 g of the benzoic acid. Total yield=2.02 g (20%). 1H NMR (400 MHz, CD3OD): 8.13 (d, J=1.6, 1H), 8.01 (dd, J=8.1, 1.6, 1H), 7.50 (d, J=8.1, 1H).

Reference： [1]Patent: US2006/69286,2006,A1 .Location in patent: Page/Page column 26
[2]Patent: WO2010/65134,2010,A1 .Location in patent: Page/Page column 58
[3]Journal of Medicinal Chemistry,2006,vol. 49,p. 6371 - 6390
[4]Patent: US2004/224983,2004,A1 .Location in patent: Page 13 - 14
[5]Patent: US2005/38032,2005,A1 .Location in patent: Page/Page column 14
[6]Patent: US2006/69286,2006,A1 .Location in patent: Page/Page column 51
[7]Chemische Berichte,1924,vol. 57,p. 2125
[8]Organic Process Research and Development,2006,vol. 10,p. 1287 - 1291

2
[ 116529-62-5 ]
[ 20776-54-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With tin(ll) chloride; In ethyl acetate; at 20℃; for 16.0h;	B. 2-Amino-4-iodo-benzoic acid. ; 4-lodo-2-nitro-benzoic acid (20 g, 68 mmol, 1.0 equiv.) was dissolved in 200 mL of EtOAc and then SnCl2.2H2O (46 g, 204 mmol, 3.0 equiv.) was added in three portions. The reaction mixture was stirred at rt for 16 h. Satd. aq. NaHCO3 was carefully added to adjust the mixture to pH=9. The precipitated solid was removed by filtration through diatomaceous earth, washing with water. The aqueous layer in the filtrate was separated and acidified with conc. HCl to pH=2. The precipitated solid was collected by filtration and dried to afford the title compound as white solid (19 g, 68 mmol, 100%). 1H NMR (400 MHz, CD3OD): 1H NMR (500 MHz, CDCl3): 7.56 (d, J=8.5, 1H), 7.08 (s, 1H), 6.99 (d, J=8.5, 1H), 5.71 (br s, 2H).

Reference： [1]Patent: US2006/69286,2006,A1 .Location in patent: Page/Page column 26
[2]American Chemical Journal,1910,vol. 44,p. 448

3
[ 7664-93-9 ]
[ 41252-97-5 ]
[ 108-24-7 ]
[ 64-19-7 ]
chromic acid [ No CAS ]
[ 116529-62-5 ]

Reference： [1]Chemische Berichte,1924,vol. 57,p. 2125

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; potassium iodide

5
[ 116529-62-5 ]
[ 7664-41-7 ]
iron(II) sulfate [ No CAS ]
[ 20776-54-9 ]

Reference： [1]American Chemical Journal,1910,vol. 44,p. 448

6
[ 116529-62-5 ]
4-iodo-2-nitrobenzoyl chloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride for 0.75h; Heating;
	With thionyl chloride for 0.75h; Heating / reflux;	6.B B. 4-Iodo-2-nitrobenzoic acid piperidine amide A suspension of 4-iodo-2-nitrobenzoic acid (1.0 g, 3.4 mmol) in thionyl chloride (10 mL) was heated to reflux for 45 min. The reaction mixture became homogeneous. The mixture was cooled and concentrated in vacuo to give 4-iodo-2-nitrobenzoyl chloride as a yellow oil, which was used immediately in the following reaction. 1H NMR (500 MHz, CDCl3): 8.38 (d, J=1.6 Hz, 1H), 8.12 (dd, J=8.1, 1.6 Hz, 1H), 7.48 (d, J=8.1 Hz, 1H). To a solution of 4-iodo-2-nitrobenzoyl chloride (3.4 mmol) in DCM (10 mL) at ambient temperature was added piperidine (1.3 mL, 13.1 mmol). The reaction mixture was stirred for 0.5 h then poured into 1 N HCl and extracted with DCM (2). The combined organic extracts were dried (Na2SO4), and concentrated in vacuo affording the title amide as a white solid (1.2 g, 98%). MS (ESI): m/z 361 [M+H]+, 383 [M+Na]+. 1H NMR (400 MHz, CDCl3): (rotameric broadening) 8.51 (d, J=1.6 Hz, 1H), 8.01 (dd, J=8.0, 1.6 Hz, 1H), 7.12 (d, J=8.0 Hz, 1H), 3.85-3.65 (bm, 2H), 3.16 (t, J=5.6 Hz, 2H), 1.90-1.35 (bm, 6H).

Reference： [1]Allison, Brett D.; Phuong, Victor K.; McAtee, Laura C.; Rosen, Mark; Morton, Magda; Prendergas, Clodagh; Barrett, Terry; Lagaud, Guy; Freedman, Jamie; Li, Na; Wu, Xiaodong; Venkatesan, Hariharan; Pippel, Marna; Woods, Craig; Rizzolio, Michèle C.; Hack, Michael; Hoey, Kenway; Deng, Xiaohu; King, Christopher; Shankley, Nigel P.; Rabinowitz, Michael H. [Journal of Medicinal Chemistry, 2006, vol. 49, # 21, p. 6371 - 6390]
[2]Current Patent Assignee: JOHNSON & JOHNSON INC - US2004/224983, 2004, A1 Location in patent: Page 14

7
[ 116529-62-5 ]
[ 74-88-4 ]
methyl 2-nitro-4-iodobenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 0 - 20℃;	1.2 Step 2: Methyl 4-iodo-2-nitrobenzoate; To a solution of 4-iodo-2-nitrobenzoic acid (2.3 g, 7.9 mmol) in DMF (30 mL) was added DBU (2.4 mL, 16 mmol) followed by iodomethane (1.5 mL, 24 mmol). The reaction mixture was allowed to stir at 0 0C for 15 min, then slowly allowed to warm to rt and to stir overnight. After 12 h, the reaction mixture was poured into 200 mL Of H2O and extracted with EtOAc (2 x 100 mL). The organic solutions were combined, washed with H2O (2 x 100 mL), dried over Na2SO4, filtered and concentrated to give methyl 4-iodo-2-nitrobenzoate (2.3 g, 96%).
95%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide at 0 - 20℃;
95%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In DMF (N,N-dimethyl-formamide) at 0 - 20℃;	4.B B. Methyl 2-amino-4-iodobenzoate. To a stirred solution of 4-iodo-2-nitrobenzoic acid (2.3 g, 7.9 mmol) in DMF (30 mL) at 0° C. was added DBU (2.4 mL, 16 mmol) followed by iodomethane (1.5 mL, 24 mmol). The reaction mixture was stirred 15 min at 0° C., then was allowed to warm to room temperature and was stirred overnight. The mixture was poured into H2O and extracted with EtOAc (2). The combined organic extracts were washed with H2O (2), dried (MgSO4), and concentrated in vacuo. The residue was purified by flash chromatography (hexanes/EtOAc) to afford methyl 4-iodo-2-nitrobenzoate as a pale yellow solid (2.30 g, 95%). To a solution of the nitrobenzoate (2.3 g, 7.4 mmol) in 1:1 EtOAc/DCM (10 mL) at room temperature was added SnCl2.2H2O (8.3 g, 37 mmol). The reaction mixture was allowed to stir overnight. The solvents were evaporated in vacuo, and the residue was partitioned between satd. aq. NaHCO3 and DCM. The layers were separated, and the aqueous layer was further extracted with DCM (2×). The combined organic layers were dried (MgSO4) and concentrated in vacuo to provide the pure aminobenzoate as a yellow solid (1.87 g, 91%). 1H NMR (500 MHz, CDCl3): 7.52 (d, J=8.5 Hz, 1H), 7.07 (d, J=1.6 Hz, 1H), 6.96 (dd, J=8.5, 1.6 Hz, 1H), 5.72 (br s, 2H), 3.86 (s, 3H).

Reference： [1]Current Patent Assignee: TAKEDA PHARMACEUTICAL COMPANY LIMITED - WO2010/65134, 2010, A1 Location in patent: Page/Page column 58-59
[2]Allison, Brett D.; Phuong, Victor K.; McAtee, Laura C.; Rosen, Mark; Morton, Magda; Prendergas, Clodagh; Barrett, Terry; Lagaud, Guy; Freedman, Jamie; Li, Na; Wu, Xiaodong; Venkatesan, Hariharan; Pippel, Marna; Woods, Craig; Rizzolio, Michèle C.; Hack, Michael; Hoey, Kenway; Deng, Xiaohu; King, Christopher; Shankley, Nigel P.; Rabinowitz, Michael H. [Journal of Medicinal Chemistry, 2006, vol. 49, # 21, p. 6371 - 6390]
[3]Current Patent Assignee: JOHNSON & JOHNSON INC - US2005/38032, 2005, A1 Location in patent: Page/Page column 14

8
[ 116529-62-5 ]
[ 35674-20-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ferrosulfate; ammonia 2: diluted KOH-solution; iodine 3: sulfuric acid; alcohol; sodium nitrite / Diazotization

Reference： [1]Wheeler; Johns [American Chemical Journal, 1910, vol. 44, p. 448]

9
[ 116529-62-5 ]
2-ethylamino-4-iodo-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: ferrosulfate; ammonia 2: alcoholic KOH-solution

Reference： [1]Wheeler; Johns [American Chemical Journal, 1910, vol. 44, p. 448]

10
[ 116529-62-5 ]
[ 35674-29-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: ferrosulfate; ammonia 2: diluted KOH-solution; iodine

Reference： [1]Wheeler; Johns [American Chemical Journal, 1910, vol. 44, p. 448]

11
[ 116529-62-5 ]
[ 116529-53-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ferrosulfate; ammonia 2: diluted KOH-solution; iodine 3: hydrogen chloride
	Multi-step reaction with 3 steps 1: ferrosulfate; ammonia 2: diluted KOH-solution; iodine 3: alcoholic KOH-solution

Reference： [1]Wheeler; Johns [American Chemical Journal, 1910, vol. 44, p. 448]
[2]Wheeler; Johns [American Chemical Journal, 1910, vol. 44, p. 448]

12
[ 116529-62-5 ]
4-iodo-2-methylamino-benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: ferrosulfate; ammonia 2: alcoholic KOH-solution

Reference： [1]Wheeler; Johns [American Chemical Journal, 1910, vol. 44, p. 448]

13
[ 4727-72-4 ]
[ 116529-62-5 ]
1-benzyl-piperidin-4-yl 4-iodo-2-nitro-benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In oxalyl dichloride; toluene	42.e 1-Benzyl-piperidin-4-yl 4-iodo-2-nitro-benzoate e) 2.33 g (0.00795 mol) of 4-iodo-2-nitrobenzoic acid were boiled und reflux in 13.8 ml (0.16 mol) of oxalyl chloride for 3 hrs. After removal of the excess oxalyl chloride the mixture was concentrated twice with 30 ml of toluene each time. The residue was dissolved in 80 ml of toluene, treated with 1.94 ml (0.0139 mol) of triethylamine and 1.52 g (0.00795 mol) of 1-benzyl-4-hydroxypiperidine and boiled at reflux for 18 hrs. After removal of the solvent the residue was chromatographed on silica gel with ethyl acetate/hexane (1:3). 0.465 g (13%) of 1-benzyl-piperidin-4-yl 4-iodo-2-nitrobenzoate was obtained as a yellow oil. MS: me/e=467 (C19 H20 IN2 O4 +).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US5753679, 1998, A

14
[ 610-36-6 ]
[ 116529-62-5 ]

Yield	Reaction Conditions	Operation in experiment
	With Ki; sodium nitrite; In water;	d) 1.92 g (0.0105 mol) of <strong>[610-36-6]4-amino-2-nitrobenzoic acid</strong> were suspended in 105 ml of water, treated with 2.6 ml of 37% HCI and cooled to 0 C. A solution of 0.87 g (0.0126 mol) of NaNO2 in 2.5 ml of water was added. After stirring for 5 min. a solution of 2.1 g (0.0126 mol) of KI in 3.1 ml of water was added. The reaction mixture was stirred at room temperature for 1 hr. and excess iodine was destroyed with NaHSO3 solution. The mixture was extracted with ethyl acetate and the organic phase was washed with saturated sodium chloride solution and dried over Na2 SO4. After removal of the solvent and drying 1.84 g (60%) of 4-iodo-2-nitrobenzoic acid were obtained as brown crystals. MS: me/e (% basic peak)=292 (C7 H3 INO2 --, 78.5), 248 (100).

Reference： [1]Patent: US5753679,1998,A

15
[ 1201806-96-3 ]
[ 116529-62-5 ]
[ 1201807-00-2 ]

Yield	Reaction Conditions	Operation in experiment
62%	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran at 20℃; for 15h; Inert atmosphere;

Reference： [1]Pierrat, Philippe; Rethore, Celine; Muller, Thierry; Braese, Stefan [Chemistry - A European Journal, 2009, vol. 15, # 43, p. 11458 - 11460]

16
[ 173522-95-7 ]
[ 116529-62-5 ]
(S)-2-(2-nitro-4-iodo-benzoylamino)-3-(3,4-dichloro-phenyl)-propionic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%		B. (S)-2-2-Amino-4-iodo-benzoylamino)-3-(3,4-dichloro-phenyl)-propionic acid methyl ester.; A solution of 4-iodo-2-nitrobenzoic acid (0.35 g, 1.20 mmol) dissolved in SOCl2 (5 mL) was heated at reflux for 2 h. The mixture was concentrated and the resulting liquid was dissolved in DMF (5 mL). DMAP (161 mg, 1.32 mmol) and 2-amino-3-(3,4-dichloro-phenyl)-propionic acid methyl ester hydrochloride (0.37 g, 1.32 mmol) were added and the solution was stirred overnight at rt. The mixture was poured into water and extracted with EtOAc (3×). The organic layers were combined, dried (MgSO4), and concentrated to provide the crude product as a yellow oil. The oil was purified by flash chromatography (hexanes/EtOAc) to provide the product as a colorless oil (50%, 313 mg). 1H NMR (400 MHz, CDCl3): 7.59 (d, J=8.1, 2H), 7.37(d, J=8.2, 1H), 7.28 (d, J=2.0, 1H), 7.18 (d, J=8.0, 1H), 7.04 (dd, J=8.2, 2.0, 1H), 6.49 (d, J=7.4, 1H), 5.10-5.04 (m, 1H), 3.81 (s, 3H), 3.33-3.17 (m, 2H).

Reference： [1]Patent: US2006/69286,2006,A1 .Location in patent: Page/Page column 18

17
[ 116529-62-5 ]
N-(3-fluorophenyl)-2-(3-((7-iodoquinazolin-4-yl)amino)-1H-pyrazol-5-yl)ethanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tin(II) chloride dihdyrate / ethyl acetate / 20 °C 2: 2-methoxy-ethanol / 130 °C / Inert atmosphere 3: trichlorophosphate / 3 h / 110 °C / Inert atmosphere 4: isopropyl alcohol / 1 h / 90 °C / Inert atmosphere