[ CAS No. 693-93-6 ] {[proInfo.proName]}

Name: 693-93-6|4-Methyloxazole|97%
Brand: Ambeed
SKU: A140742
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Quality Control of [ 693-93-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 693-93-6 ]

SDS Specification

Alternatived Products of [ 693-93-6 ]

Product Details of [ 693-93-6 ]

CAS No. :	693-93-6	MDL No. :	MFCD11110237
Formula :	C₄H₅NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PUMREIFKTMLCAF-UHFFFAOYSA-N
M.W :	83.09	Pubchem ID :	69663
Synonyms :

Calculated chemistry of [ 693-93-6 ]

Physicochemical Properties

Num. heavy atoms :	6
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.25
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	21.47
TPSA :	26.03 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.28 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.44
Log Po/w (XLOGP3) :	0.74
Log Po/w (WLOGP) :	0.98
Log Po/w (MLOGP) :	-0.47
Log Po/w (SILICOS-IT) :	1.43
Consensus Log Po/w :	0.82

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.44
Solubility :	3.03 mg/ml ; 0.0365 mol/l
Class :	Very soluble
Log S (Ali) :	-0.87
Solubility :	11.3 mg/ml ; 0.136 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.51
Solubility :	2.55 mg/ml ; 0.0307 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.68

Safety of [ 693-93-6 ]

Signal Word:	Danger	Class:	8,3
Precautionary Statements:	P501-P240-P210-P233-P243-P241-P242-P280-P370+P378-P303+P361+P353-P305+P351+P338+P310-P403+P235	UN#:	2920
Hazard Statements:	H225-H318	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 693-93-6 ]

* 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 [ 693-93-6 ]
Downstream synthetic route of [ 693-93-6 ]

[ 693-93-6 ] Synthesis Path-Upstream 1~7

1
[ 116-09-6 ]
[ 693-93-6 ]

Reference： [1] Patent: US4039554, 1977, A,
[2] Patent: US4039554, 1977, A,

2
[ 4128-31-8 ]
[ 116-09-6 ]
[ 693-93-6 ]

Reference： [1] Patent: US4039554, 1977, A,

3
[ 583-59-5 ]
[ 116-09-6 ]
[ 693-93-6 ]

Reference： [1] Patent: US4039554, 1977, A,

4
[ 116-09-6 ]
[ 693-93-6 ]

Reference： [1] Patent: US4039554, 1977, A,
[2] Patent: US4039554, 1977, A,

5
[ 116-09-6 ]
[ 693-93-6 ]

Reference： [1] Patent: US4039554, 1977, A,
[2] Patent: US4039554, 1977, A,

6
[ 2510-32-9 ]
[ 693-93-6 ]

Reference： [1] Journal of the Chemical Society, 1953, p. 93,95

7
[ 693-93-6 ]
[ 41409-84-1 ]
[ 1006-21-9 ]

Reference： [1] Liebigs Annalen der Chemie, 1979, vol. 1, # 11, p. 1657 - 1664

[ 693-93-6 ] Synthesis Path-Downstream 1~65

1
[ 693-93-6 ]
[ 2908-71-6 ]
3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-oxazolium; bromide [ No CAS ]

Reference： [1]Journal of Biological Chemistry,1959,vol. 234,p. 738 - 741

2
[ 2510-32-9 ]
[ 693-93-6 ]

Reference： [1]European Journal of Organic Chemistry,2019,vol. 2019,p. 2884 - 2898
[2]Journal of the Chemical Society,1953,p. 93,95

3
[ 693-93-6 ]
[ 41649-08-5 ]
[ 1622-73-7 ]

Reference： [1]Liebigs Annalen der Chemie,1979,vol. 1,p. 1657 - 1664

4
[ 693-93-6 ]
[ 41409-84-1 ]
[ 1006-21-9 ]

Reference： [1]Liebigs Annalen der Chemie,1979,vol. 1,p. 1657 - 1664

5
[ 693-93-6 ]
[ 626-55-1 ]
[ 118559-26-5 ]

Reference： [1]Synthesis,1987,p. 693 - 696

6
[ 693-93-6 ]
[ 110-65-6 ]
[ 14496-24-3 ]

Reference： [1]Liebigs Annalen der Chemie,1981,p. 668 - 682

7
[ 693-93-6 ]
[ 4394-85-8 ]
4-methyl-5-oxazolecarboxaldehyde [ No CAS ]

Reference： [1]Gazzetta Chimica Italiana,1988,vol. 118,p. 211 - 232

8
[ 693-93-6 ]
[ 3731-38-2 ]
[ 122829-26-9 ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium; ammonium chloride; In tetrahydrofuran; hexane; ethyl acetate;	EXAMPLE 3 3-Hydroxy-3-[2-(4-methyl-1,3-oxazol)-yl]quinuclidine A solution of n-butyllithium in hexane (1.6M, 50 ml, 80 mmol) was added dropwise over 30 min to a stirred solution of <strong>[693-93-6]<strong>[693-93-6]4-methyloxazol</strong>e</strong> (7.26 g, 87.5 mmol) in tetrahydrofuran (80 ml) under nitrogen, keeping the temperature below -65. After a further 30 min at -70, a solution of quinuclidin-3-one (9.10 g, 72.8 mmol) in tetrahydrofuran (20 ml) was added over 5 min. The mixture was kept at -70 for 2 h, then warmed to 25 overnight. Saturated ammonium chloride solution (50 ml) was added, the organic layer separated, and the aqueous layer extracted three times with dichloromethane. The combined organic layers were dried over potassium carbonate and evaporated. The residue was dissolved in boiling ethyl acetate (250 ml), filtered and concentrated to 100 ml. The product crystallized on cooling as colourless prisms (4.98 g, 33%), m.p. 176-177 . (Found: C, 63.25; H, 7.73; N, 13.40. C11 H16 N2 O2 requires: C, 63.44; H, 7.74; N, 13.45%) nu max; 3200-2500 (br), 1600, 1550; m/e; 208 (M+); delta (CDCl3); 1.32-1.57 (3H, m, 5CH and 8CH2); 2.11-2.19 (2H, m, 4CH and 5CH); 2.17 (3H, d, J=1 Hz, CH3); 2.76-2.88 (3H, m. 6CH2 and 7CH); 2.94-3.01 (1H, m, 7CH); 2.96 (1H, dd, J=1 Hz and 14 Hz, 2CH); 3.78 (1H, dd, J=2 Hz and 14 Hz, 2CH); 7.35 (1H, q, J=1 Hz, oxazole-H).

Reference： [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 1128 - 1138
[2]Patent: US5324723,1994,A

9
[ 693-93-6 ]
[ 75-77-4 ]
[ 90892-92-5 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1984,p. 258 - 260
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3413 - 3420

10
[ 693-93-6 ]
[ 75-77-4 ]
[ 90892-92-5 ]
[ 108665-42-5 ]

Reference： [1]Journal of Organic Chemistry,1987,vol. 52,p. 3413 - 3420

11
[ 693-93-6 ]
[ 591-50-4 ]
[ 877-39-4 ]

Reference： [1]Synthesis,1987,p. 693 - 696

12
[ 693-93-6 ]
[ 815-52-1 ]
[ 109308-43-2 ]
[ 109308-56-7 ]

Reference： [1]Chemische Berichte,1987,vol. 120,p. 1815 - 1824

13
[ 693-93-6 ]
[ 22537-06-0 ]
[ 78520-05-5 ]

Reference： [1]Liebigs Annalen der Chemie,1981,p. 668 - 682

14
[ 693-93-6 ]
[ 661-54-1 ]
[ 56286-84-1 ]
[ 75-05-8 ]

Reference： [1]Chemical and pharmaceutical bulletin,1985,vol. 33,p. 3670 - 3674

15
[ 693-93-6 ]
[ 1573-17-7 ]
[ 30614-73-4 ]

Reference： [1]Liebigs Annalen der Chemie,1981,p. 668 - 682

16
[ 693-93-6 ]
[ 580-13-2 ]
[ 118559-27-6 ]

Reference： [1]Synthesis,1987,p. 693 - 696

17
[ 693-93-6 ]
[ 4591-28-0 ]
[ 91190-48-6 ]

Reference： [1]Journal of Organic Chemistry,1984,vol. 49,p. 3478 - 3483

18
[ 693-93-6 ]
[ 99-90-1 ]
[ 118559-25-4 ]

Reference： [1]Synthesis,1987,p. 693 - 696

19
[ 693-93-6 ]
[ 83662-44-6 ]
[ 104462-97-7 ]

Reference： [1]Chemische Berichte,1986,vol. 119,p. 3607 - 3630

20
[ 693-93-6 ]
[ 83662-44-6 ]
[ 104462-97-7 ]
[ 75-05-8 ]

Reference： [1]Bulletin des Societes Chimiques Belges,1984,vol. 93,p. 241 - 260

21
[ 693-93-6 ]
[ 100-52-7 ]
[ 90892-90-3 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1984,p. 258 - 260
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3413 - 3420

22
[ 693-93-6 ]
[ 80866-48-4 ]
[ 104462-89-7 ]

Reference： [1]Chemische Berichte,1986,vol. 119,p. 3607 - 3630

23
[ 693-93-6 ]
[ 80866-48-4 ]
[ 104462-89-7 ]
[ 75-05-8 ]

Reference： [1]Bulletin des Societes Chimiques Belges,1984,vol. 93,p. 241 - 260

24
[ 693-93-6 ]
[ 75-36-5 ]
[ 90892-91-4 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1984,p. 258 - 260
[2]Journal of Organic Chemistry,1987,vol. 52,p. 3413 - 3420

25
[ 693-93-6 ]
[ 501-65-5 ]
[ 954-54-1 ]

Reference： [1]Liebigs Annalen der Chemie,1981,p. 668 - 682

26
[ 693-93-6 ]
[ 104462-87-5 ]
[ 104462-98-8 ]

Reference： [1]Chemische Berichte,1986,vol. 119,p. 3607 - 3630

27
[ 693-93-6 ]
[ 762-21-0 ]
[ 30614-77-8 ]

Reference： [1]Liebigs Annalen der Chemie,1981,p. 668 - 682

28
[ 693-93-6 ]
[ 74-86-2 ]
[ 110-00-9 ]

Reference： [1]Liebigs Annalen der Chemie,1981,p. 668 - 682
[2]Liebigs Annalen der Chemie,1981,p. 668 - 682

29
[ 693-93-6 ]
[ 68-12-2 ]
4-methyl-5-oxazolecarboxaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of compound 2A (4.5 g, 54.2 mmol) in 60 mL of dry THF at -78 C under a nitrogen atmosphere was added 1.1 equiv. of n-BuLi (2.5 M in THF) in THF and the reaction was allowed to stir for 45 minutes. DMF (3.96 g, 54.2 mmol) was added, and the reaction was allowed to stand overnight and warm to room temperature. The reaction mixture was then neutralized with 2N HC1 and extracted with DCM (50 mL). The organic combined phases were combined, dried over Na2S04, filtered, and concentrated in vacuo to provide intermediate compound 2B, which was used without further purification.

Reference： [1]European Journal of Organic Chemistry,2018,vol. 2018,p. 515 - 524
[2]Heterocycles,1994,vol. 38,p. 1791 - 1796
[3]Patent: WO2018/35005,2018,A1 .Location in patent: Page/Page column 36

30
[ 693-93-6 ]
[ 68-12-2 ]
4-methyl-5-oxazolecarboxaldehyde [ No CAS ]
[ 159015-06-2 ]

Reference： [1]Heterocycles,1994,vol. 38,p. 1791 - 1796

31
[ 693-93-6 ]
[ 10192-66-2 ]
[ 187467-61-4 ]
3-[3-(1,5-dihydro-9-hydroxy-8-methyl-3H-[1,3]dioxepino[5,6-c]pyridin-3-yl)-propyl]-1,5-dihydro-9-hydroxy-8-methyl-3H-[1,3]dioxepino[5,6-c]pyridine [ No CAS ]

Reference： [1]Croatica Chemica Acta,1996,vol. 69,p. 1561 - 1576

32
[ 693-93-6 ]
4,7-dihydro-2-(4,7-dihydro-1,3-dioxepin-2-yl)-5-nitro-1,3-dioxepin [ No CAS ]
[ 187467-53-4 ]

Reference： [1]Croatica Chemica Acta,1996,vol. 69,p. 1561 - 1576

Yield	Reaction Conditions	Operation in experiment
		EXAMPLES 27 The method used is analogous to Example 2 (b), with 36.4 parts of N,N-dimethylaniline in place of N,N-diethylaniline. The yield of 4-methyloxazole is 5.2 parts (62% of theory), of boiling point 88 C.
		EXAMPLE 28 The method used is analogous to Example 2 (b), with 38.7 parts of quinoline in place of N,N-diethylaniline. The yield of 4-methyloxazole is 4 parts (48% of theory), of boiling point 88 C.

35
[ 693-93-6 ]
[ 910552-65-7 ]
8-(1-ethyl-propyl)-2,6-dimethyl-3-(4-methyl-oxazol-5-yl)-imidazo[1,2-b]pyridazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
39%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); triphenylphosphine; In N,N-dimethyl-formamide; at 130℃;	Example 50.; Preparation of 8-( 1 -ethyl-propyl)-2,6-dimethyl-3-(4-methyl-oxazol-5-yl)-imidazo[1,2- b]pyridazine.; 686 mg of 8-(1-Ethyl-propyl)-3-iodo-2,6-dimethyl-imidazo[1,2-b]pyridazine (2.0 mmol), 830 mg of <strong>[693-93-6]4-methyl-oxazole</strong>. (10 mmol), 105 mg of triphenylphosphine ( 0.4 mmol) and 1.30 g of cesium carbonate (4.0 mmol) are placed into tube with 10 ml of dry EPO <DP n="60"/>DMF. N2 gas is bubbled in for 20min and 92 mg of Pd2dba3 (0.1 mmol) is added. The tube is sealed and heated at 130C overnight. After being cooled to room temperature, water and CHCl2 are added to the mixture. The CHCl2 layer is separated, washed with sat. NaCl , dried over Na2SO4 and evaporated. The crude product is applied onto a silica- gel chromatography column (Hexane:AcOEt=5:l) to give 234 mg of the title product. Yield 39%. mass spectrum (m/e):299(M+l). 1H-NMR (CDCl3): 8.06 (s, 1H), 6.75 (s, 1H), 3.34 (m, 1H), 2.56 (s, 3H), 2.50 (s, 3H), 2.29 (s, 3H), 1.86 (m, 4H), 0.90 (t, J=7.4Hz, 6H).

Reference： [1]Patent: WO2006/102194,2006,A1 .Location in patent: Page/Page column 58-59

36
[ 4128-31-8 ]
[ 116-09-6 ]
[ 693-93-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; hydrogen isocyanide; In N,N-dimethyl-aniline; 1,2-dichloro-benzene;	EXAMPLE 25 13.5 Parts of hydrogen cyanide are passed into a solution of 65 parts of 2-octanol in 45 parts by volume of o-dichlorobenzene at 0 C., and 20 parts of hydrogen chloride are then passed in at +20 C., whilst cooling. The viscous mixture is stirred for 30 minutes at 20 C. 18.5 parts of hydroxyacetone and 91 parts of N,N-dimethylaniline are then added at +10 C. and the mixture is heated at 75 C. for 1 hour. At the same temperature, 150 parts of 20% strength by weight aqueous sodium hydroxide solution are added, the mixture is cooled to room temperature, the organic phase is separated off and the 4-methyloxazole formed is distilled at atmospheric pressure (boiling point 88 C.). Yield: 10.4 parts (50% of theory).

Reference： [1]Patent: US4039554,1977,A

37
[ 116-09-6 ]
[ 693-93-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N,N-diethylaniline;	b. Preparation of 4-methyloxazole: the hydrochloride obtained is added a little at a time to a solution of 29 parts of hydroxyacetone and 180 parts of N,N-diethylaniline at from 15 to 20 C. The mixture is then slowly heated to 90 C. and the 4-methyloxazole formed is distilled at 20 mm Hg into a cooled receiver. Fractional distillation gives 14.5 parts (44% of theory) of 4-methyloxazole of boiling point 88 - 89 C.
	With hydrogenchloride; hydrogen isocyanide; In N,N-dimethyl-aniline; nitrobenzene; cyclohexanol;	EXAMPLE 24 13.5 Parts of hydrogen cyanide are passed into a solution of 50.1 parts of cyclohexanol is 45 parts by volume of nitrobenzene at 0 C. and 20 parts of hydrogen chloride are then passed in at +20 C., whilst cooling. The resulting suspension is stirred for 30 minutes at 20 C. 18.5 parts of hydroxyacetone in 91 parts of N,N-dimethylaniline are then added at +10 C. and the mixture is heated to 75 C. At the same time the 4-methyl-oxazole formed is distilled at 20 mm Hg into a cooled receiver. 11.5 parts (55% of theory) of 4-methyloxazole, of boiling point 88 C., are obtained.

Reference： [1]Patent: US4039554,1977,A
[2]Patent: US4039554,1977,A

38
[ 583-59-5 ]
[ 116-09-6 ]
[ 693-93-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; hydrogen isocyanide; In dichloromethane; N,N-dimethyl-aniline;	EXAMPLE 23 13.5 Parts of hydrogen cyanide are passed into a solution of 57 parts of 2-methylcyclohexanol in 135 parts by volume of methylene chloride at -10 C., and 20 parts of hydrogen chloride are then passed in at +20 C., whilst cooling. The mixture is stirred for 45 minutes at room temperature. Methylene chloride is then stripped off under reduced pressure until the residue is viscous but can still be stirred. 18.5 parts of hydroxyacetone and 91 parts of N,N-dimethylaniline are added at +10 C. and the mixture is heated to 75 C. At the same time the 4-methyloxazole formed, and the residual methylene chloride, are distilled under reduced pressure into a cooled receiver. 15.8 parts (76% of theory) of 4-methyloxazole, of boiling point 88 C., are obtained after fractional distillation.

Reference： [1]Patent: US4039554,1977,A

39
formimido-cyclohexyl ester hydrochloride [ No CAS ]
[ 116-09-6 ]
[ 693-93-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N,N-diethylaniline;	b. Preparation of 4-methyloxazole: 32.7 parts of formimido-cyclohexyl ester hydrochloride are added, a little at a time, to a solution of 7.4 parts of hydroxyacetone and 45 parts of N,N-diethylaniline at 15 C. The mixture is slowly heated to 70 C. and the 4-methyloxazole formed is distilled at 20 mm Hg into a cooled receiver. Yield 5 parts (60% of theory) of 4-methyloxazole of boiling point 88 - 89 C.
	With 1-methyl-pyrrolidin-2-one; N,N-diethylaniline;	EXAMPLE 29 16.4 Parts of formimido-cyclohexyl ester hydrochloride are introduced into a solution of 3.7 parts of hydroxyacetone, 14.9 parts of N,N-diethylaniline and 25 parts of N-methylpyrrolidone at -25 C. The mixture is then heated to 70 C and the 4-methyloxazole formed is distilled at C. 20 mm Hg into a cooled receiver. Yield, 4.7 parts (56% of theory), of boiling point 88 C.

Reference： [1]Patent: US4039554,1977,A
[2]Patent: US4039554,1977,A

40
formimido-cyclohexyl ester [ No CAS ]
[ 116-09-6 ]
[ 693-93-6 ]

Yield	Reaction Conditions	Operation in experiment
		b. Preparation of 4-methyloxazole: a mixture of 6.4 parts of formimido-cyclohexyl ester and 3.7 parts of hydroxy-acetone is heated to 150 C. in the course of 30 minutes. At the same time the 4-methyloxazole formed is distilled off. 0.5 part of 4-methyloxazole of boiling point 88.5 C. is obtained.
	With chloroacetic acid;	EXAMPLE 22 A mixture of 6.4 parts of formimido-cyclohexyl ester, 4.75 parts of chloroacetic acid and 3.7 parts of hydroxyacetone is heated at 60 C. for 1 hour. At the same time the 4-methyloxazole formed is distilled at 20 mm Hg into a cooled receiver. After fractionation, 1.2 parts (27% of theory) of 4-methyloxazole of boiling point 88 C. are obtained.

Reference： [1]Patent: US4039554,1977,A
[2]Patent: US4039554,1977,A

41
[ 693-93-6 ]
[ 7789-45-9 ]
bis[dibromobis(4-methyloxazole)copper(II)] [ No CAS ]

Reference： [1]Inorganica Chimica Acta,1982,vol. 59,p. 19 - 24

42
[ 693-93-6 ]
copper dichloride [ No CAS ]
di-μ-chloro-bis[chlorobis(4-methyloxazole)copper(II)] [ No CAS ]

Reference： [1]Inorganica Chimica Acta,1983,vol. 70,p. 137 - 142

43
[ 693-93-6 ]
[ 833451-96-0 ]
[3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)phenyl]-(4-methyl-oxazol-2-yl) methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Step B: Synthesis of [3. 4-DIFLUORO-2-(2-FLUORO-4-IODO-PHENVLAMINO)-PHENVL1-(4-METHVL- oxazol-2-yl)-methanone. A solution of <strong>[693-93-6]4-methyl-oxazole</strong> (0.080 mL, 1.0 MMOL) in tetrahydrofuran (10 mL) was cooled to-78 C and treated with n-butyllithium (1.6 M in hexane, 0.51 mL, 0.81 MMOL). The resultant solution was stirred 25 min at-78 C. Zinc chloride (1.45 mL, 1.0 M in ether) was added and the reaction mixture was allowed to warm to 0 C over 45 min. Copper (I) iodide (185 mg, 0.97 MMOL) was added and the reaction was stirred for 10 min. 3, 4-DIFLUORO-2- (2- fluoro-4-iodo-phenylamino)-benzoyl chloride (200 mg, 0.49 mmol) was added and the reaction mixture was allowed to warm to ambient temperature overnight. The reaction was diluted with ethyl acetate and was washed with concentrated ammonium hydroxide-water (1: 1,40 mL), water (40 mL) and brine (40 mL). The organics were concentrated in vacuo and chromatographed on silica gel. Elution with hexanes ethyl acetate (gradient to 20% ethyl acetate) afforded [3, 4-DIFLUORO-2- (2-FLUORO-4-IODO-PHENYLAMINO)-PHENYL]- (4-METHYL-OXAZOL-2- yl)-methanone (21 mg) after crystallization from dichlormethane-hexanes : m. p. 127 C ; 1H NMR (400 MHz, CDCL3) No. 9.59 (s, 1 H), 8.56 (ddd, J = 9.3, 5.8, 2.1 Hz, 1 H), 7.62 (d, J = 1.2 Hz, 1 H), 7.40 (dd, J = 10.3, 2.0 Hz, 1 H), 7.34 (br d, J = 8.6 Hz, 1 H), 6.86 (dt, J = 7.1, 9.2 Hz, 1 H), 6.69 (dt, J = 4.9, 8.7 Hz, 1 H), 2.30 (d, J = 1.2 Hz, 3 H) ; 19F NMR (376 MHz, CDCl3) 8-125. 7, -125.9,-143. 2; MS (APCI+) = 459.0. Anal. CALCD/FOUND for C17H10F3IN2O2No.0.1(C6H14) : C, 45.29/45. 38; H, 2.46/2. 32; N, 6.00/5. 73.

Reference： [1]Patent: WO2005/7616,2005,A1 .Location in patent: Page/Page column 22

44
[ 693-93-6 ]
[ 947145-09-7 ]
[ 947143-92-2 ]

Yield	Reaction Conditions	Operation in experiment
85%		General procedure: Butyl lithium (1.6 M in hexane, 1.46 mL, 2.34 mmol) was added drop-wise to a stirred solution of <strong>[693-93-6]<strong>[693-93-6]4-methyloxazol</strong>e</strong> (162 mg, 1.95 mmol) in THF (2 mL) at -78 C (dry ice/acetone bath). The solution was stirred at this temperature for 10 minutes then a solution of zinc chloride (797 mg, 5.85 mmol) in THF (4 mL) was added drop-wise. Solution was stirred for 15 minutes at - 78 C then cooling bath removed and reaction mixture allowed to warm to RT. The zinc oxazole solution was added via a syringe to a pre-sealed and nitrogen purged microwave vial (Biotage) containing the (2-amino-6-bromo-3-nitro-pyridin-4-yl)-(6-methyl-pyridin-3-ylmethyl)-carbamic acid ethyl ester (400 mg, 0.98 mmol) and the palladium catalyst (68 mg, 0.098 mmol). The vial was heated under microwave irradiation (Biotage, Initiator 8) for 15 minutes at 60 C. The reaction mixture was partitioned between ethyl acetate (20 mL) and a 10 % aqueous solution of ammonia (20 mL). The layers were separated and organics were washed with brine (20 mL) then dried (MgSO4) and evaporated. The crude was columned on Isco Companion on a silica column (40 g, Redisep). Eluted with ethyl acetate:methanol, increasing the gradient linearly from 100:0 to 90:10 over 10 column volumes. The title fractions were combined and evaporated to yield the title compound as a yellow gum (342 mg, 85%). 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.22 (d, J=6.64 Hz, 3 H) 2.28 (s, 3 H) 2.54 (s, 3 H) 4.08 - 4.25 (m, 2 H) 4.96 (s, 2 H) 6.36 (br. s., 2 H) 7.14 (d, J=7.82 Hz, 1 H) 7.26 (s, 1 H) 7.51 - 7.54 (m, 1 H) 7.65 - 7.71 (m, 1 H) 8.43 (s, 1 H). LRMS (ES+) m/z = 413 (MH+).
		PREPARATION 70; [2-Amino-6-(4-methyl-oxazol-2-yl )-3-nitro-pyridin-4-yl]-(6-methyl-pyridin-3-ylmethyl)-carbamic acid ethyl ester; Butyl lithium (1.6 M in hexane, 366 mul) was added drop-wise to a stirred solution of <strong>[693-93-6]<strong>[693-93-6]4-methyloxazol</strong>e</strong> (41 mg) in THF (0.5 ml) in a ReactiVial at -78 C. (dry ice/acetone bath). The solution was stirred at this temperature for 10 minutes then a solution of zinc chloride (199 mg) in THF (1 ml) was added drop-wise. The solution was stirred for 15 minutes at -78 C. then the cooling bath removed and the reaction mixture allowed to warm to room temperature. This zinc oxazole solution was then added via syringe to a pre-sealed and nitrogen purged microwave vial (Biotage, 0.5-2.0 ml) containing (2-Amino-6-bromo-3-nitro-pyridin-4-yl)-(6-methyl-pyridin-3-ylmethyl)-carbamic acid ethyl ester (100 mg) and palladium bis(triphenylphosphine)dichloride (34 mg). The vial was heated under microwave irradiation (Biotage, Initiator 8) for 15 minutes at 60 C. The reaction mixture was then partitioned between ethyl acetate (10 ml) and a saturated aqueous solution of ammonium chloride (10 ml). The layers were separated and the aqueous extracted with ethyl acetate (10 ml). The combined organics were washed with brine (10 ml) then dried (MgSO4) and evaporated. The crude was columned on Isco Companion on a silica column (12 g, Redisep), eluting with ethyl acetate for 4 column volumes (CV), then the gradient increased linearly from 0-5% methanol in ethyl acetate over 10 CV. This provided the title compound (69 mg) as a yellow gum.1H NMR (400 MHz, CHLOROFORM-d) delta ppm 1.11-1.25 (m, 3 H) 2.28 (s, 3 H) 2.56 (s, 3 H), 4.13-4.23 (m, 2 H) 4.96 (s, 2 H) 6.37 (s, 2 H) 7.16 (d, J=7.80 Hz, 1 H) 7.26 (s, 1 H) 7.53 (s, 1 H) 7.65-7.78 (m, 1 H) 8.43 (s, 1 H), LCMS Rt=1.86 m/z 413 [MH]+

Reference： [1]Tetrahedron Letters,2011,vol. 52,p. 5728 - 5732
[2]Patent: US2007/197478,2007,A1 .Location in patent: Page/Page column 56

45
[ 693-93-6 ]
C₁₄H₁₅BrN₆O₄ [ No CAS ]
[ 1340588-60-4 ]

Yield	Reaction Conditions	Operation in experiment
75%		General procedure: Butyl lithium (1.6 M in hexane, 1.46 mL, 2.34 mmol) was added drop-wise to a stirred solution of <strong>[693-93-6]<strong>[693-93-6]4-methyloxazol</strong>e</strong> (162 mg, 1.95 mmol) in THF (2 mL) at -78 C (dry ice/acetone bath). The solution was stirred at this temperature for 10 minutes then a solution of zinc chloride (797 mg, 5.85 mmol) in THF (4 mL) was added drop-wise. Solution was stirred for 15 minutes at - 78 C then cooling bath removed and reaction mixture allowed to warm to RT. The zinc oxazole solution was added via a syringe to a pre-sealed and nitrogen purged microwave vial (Biotage) containing the (2-amino-6-bromo-3-nitro-pyridin-4-yl)-(6-methyl-pyridin-3-ylmethyl)-carbamic acid ethyl ester (400 mg, 0.98 mmol) and the palladium catalyst (68 mg, 0.098 mmol). The vial was heated under microwave irradiation (Biotage, Initiator 8) for 15 minutes at 60 C. The reaction mixture was partitioned between ethyl acetate (20 mL) and a 10 % aqueous solution of ammonia (20 mL). The layers were separated and organics were washed with brine (20 mL) then dried (MgSO4) and evaporated. The crude was columned on Isco Companion on a silica column (40 g, Redisep). Eluted with ethyl acetate:methanol, increasing the gradient linearly from 100:0 to 90:10 over 10 column volumes. The title fractions were combined and evaporated to yield the title compound as a yellow gum (342 mg, 85%).