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CAS No. :	1172068-36-8	MDL No. :	MFCD12024703
Formula :	C₇H₅BrFN₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	230.04	Pubchem ID :	-
Synonyms :

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Application In Synthesis of [ 1172068-36-8 ]

* 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 [ 1172068-36-8 ]

[ 1172068-36-8 ] Synthesis Path-Downstream 1~20

1
[ 59-67-6 ]
[ 1172068-36-8 ]
[ 1172068-39-1 ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: nicotinic acid; 5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-ylamine With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine In dichloromethane at 20℃; for 1h; Stage #2: With lithium hydroxide In dichloromethane; water for 1h;	1.I [00305] Step I: A solution of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (3.0 g,13 mmol) in CH2CL (200 mL) was treated with nicotinic acid (3.2 g, 26 mmol), bis(2- oxooxazolidin-3-yl)phosphinic chloride (6.6 g, 26 mmol) and triethylamine (6.6 g, 65 mmol). The reaction was stirred at room temperature for 1 hour, and then 3M aqueous LiOH (4 mL) was added. The reaction was stirred for 1 hour, and then saturated aqueous Na2CO3 was added (200 mL). The aqueous phase was extracted with CH9CL (1 X 200 mL), and the aqueous phase was filtered. The filtered cake was dried to yield N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3- yl)nicotinamide (3.5 g, 80% yield). 1H NMR (400 MHz, (CD3^SO) δ 9.09 (d, IH), 8.72 (dd,IH), 8.32 (d. IH), 8.26 (d, IH), 7.50 (dd, IH); LCMS (APCI+) m/z 336.9 (M+H)+, Retention time = 2.19 minutes (Method 1).
54.6%	With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine In N,N-dimethyl-formamide at 20℃; for 1h;	61 [00401] 5-Bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (0.044 g, 0.19 mmol), nicotinic acid (0.0283 g, 0.230 mmol), and BOP-Cl (0.0584 g, 0.230 mmol) were placed in DMF (3 mL) at room temperature. Triethylamine (0.133 mL, 0.956 mmol) was then added, and the reaction was stirred for 1 hour at room temperature. The reaction was then diluted with 3M LiOH (aq., 0.5 mL) and stirred for 10 minutes. The reaction was then poured into saturated Na2COs, extracted into DCM, and the organic fractions were combined, dried, filtered and concentrated to give a crude residue. The crude residue was triturated with 1 :2 MeOH/DCM to give N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.035 g, 54.6% yield) as a solid.

Reference： [1]Current Patent Assignee: PFIZER INC - WO2009/140320, 2009, A1 Location in patent: Page/Page column 88
[2]Current Patent Assignee: PFIZER INC - WO2009/89352, 2009, A1 Location in patent: Page/Page column 105

2
[ 1172068-36-8 ]
[ 403-16-7 ]
[ 1196508-96-9 ]

Yield	Reaction Conditions	Operation in experiment
71%		[00473] Step A: A solution of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H), <strong>[403-16-7]3-chloro-4-fluorobenzoic acid</strong> (319 mg, 1.83 mmol), BOP- Cl (465 mg, 1.83 mmol), and triethylamine (0.606 mL, 4.35 mmol) in DCM (5 mL) at room temperature was stirred for 2 hours. 3M aqueous LiOH (3 mL) was then added, and the mixture <n="153"/>was stirred for 10 minutes. Next, water (10 rnL) and DCM (10 rnL) were added, and the resulting precipitate was filtered. The solid isolated was triturated with 10:1 CH2CL:Me0H and filtered to provide N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-3-chloro-4- fluorobenzamide (240 mg, 71% yield) as a solid.

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 151-152

3
[ 4021-07-2 ]
[ 1172068-36-8 ]
[ 1196508-32-3 ]

Yield	Reaction Conditions	Operation in experiment
65%		00409] Step A: A solution of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H) in CH2CL (10 mL) was treated with 3-methylpicolinic acid(143 mg, 1.04 mmol), bis(2-oxooxazolidin-3-yl)phosphinic chloride (332 mg, 1.30 mmol) and triethylamine (440 mg, 4.35 mmol). The reaction was stirred at room temperature for 1 hour. The mixture was filtered to remove the product, and the filtrate was concentrated in vacuo. The residue was stirred in anhydrous THF (10 mL), treated with 2M LiOH solution (3 mL) and stirred at room temperature for 1 hour. The organic solvent was removed in vacuo, and then water (10 mL) was added. The reaction stirred for 1 hour. The solid, which separated, was filtered and washed with water and CH2CL (10 mL). The combined filtered cakes were dried to yield N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-3-methylpicolinamide (197 mg, 65percent yield). 1H NMR (400 MHz, (CD3^SO) delta 12.13 (br s, IH), 10.42 (s, IH), 8.56 (d, IH), 8.39 (d, <n="126"/>IH), 7 87 (d, IH), 7 84 (d, IH), 7.55 (dd, IH) 2.67 (s, 3H); LCMS (APCI+) m/z 349.1, 351 (M+H)+, Retention time = 3.42 minutes (Method 3).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 124-125

4
[ 86873-60-1 ]
[ 1172068-36-8 ]
[ 1196508-56-1 ]

Yield	Reaction Conditions	Operation in experiment
73%		00424] Step A: TEA (0.61 niL, 4.35 mmol) was added to 5-bromo-4-fluoro-lH- pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.87 mmol, Example 1, Step H), <strong>[86873-60-1]5-chloropicolinic acid</strong> (160 mg, 1.04 mmol) and BOP-Cl (332 mg, 1.30 mmol) in DCM (5 mL). The reaction was stirred at room temperature for 1 hour, and then a LiOH solution (2 N, 3 mL) was added. The mixture was stirred for 30 minutes, and water (10 mL) was added. The solid formed was collected by filtration, washed with DCM (10 mL) and dried to give N-(5-bromo-4-fluoro-lH- pyrrolo[2,3-b]pyridin-3-yl)-5-chloropicolinamide (240 mg, 73% yield) as a solid.

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 130

5
[ 3222-49-9 ]
[ 1172068-36-8 ]
[ 1196507-86-4 ]

Yield	Reaction Conditions	Operation in experiment
37.6%		[00363] Step A: <strong>[3222-49-9]5-Methylnicotinic acid</strong> (477 mg, 3.48 mmol), bis(2-oxooxazolidin-3- yl)phosphinic chloride (885 mg, 3.48 mmol) and triethylamine (880 mg, 8.69 mmol) were added to 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (400 mg, 1.74 mmol) in DCM (200 mL). The reaction was stirred at room temperature for 1 hour, and then 3M aqueous LiOH (4 mL) was added. The reaction was stirred for 1 hour, and then saturated aqueous Na2CO3 was added (200 mL). The aqueous phase was extracted once with DCM (200 mL), and then the aqueous phase <n="109"/>was filtered. The filtered cake was dried to yield N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin- 3-yl)-5-methylnicotinamide (228 mg, 37.6% yield) as a solid.

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 107-108

6
[ 35272-15-2 ]
[ 1172068-36-8 ]
[ 1196508-79-8 ]

Yield	Reaction Conditions	Operation in experiment
68%	With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine; In dichloromethane; at 20℃; for 1h;	00456] Step A: A mixture of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H), <strong>[35272-15-2]2-methylthiazole-4-carboxylic acid</strong> (311 mg, 2.17 mmol), and triethylamine (606 muL, 4.35 mmol) in CH2CL (10 mL) at room temperature was treated withBOP-Cl (203 mg, 2.17 mmol). After 1 hour the solid formed was filtered and washed with CH2Cl2 (3 X 4 mL) to provide N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-2- methylthiazole-4-carboxamide (210 mg, 68percent yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) delta 12.14 (s, IH), 9.83 (s, IH), 8.38 (d, IH), 8.26 (s, IH), 7.74 (d, IH), 2.77 (s, 3H); LCMS (APCI+) m/z 354.9, 356.9 (M+H)+, Retention time = 3.39 minutes (Method 2).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 144

7
[ 3222-47-7 ]
[ 1172068-36-8 ]
[ 1196507-84-2 ]

Yield	Reaction Conditions	Operation in experiment
68.5%		[00360] Step A: A mixture of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (250 mg, 1.09 mmol), <strong>[3222-47-7]6-methylnicotinic acid</strong> (313 mg, 2.28 mmol), BOP-Cl (581 mg, 2.28 mmol), and triethylamine (0.757 mL, 5.43 mmol) in DCM (5 mL) was stirred at room temperature for 30 minutes. 3M LiOH (3 mL) was then added. The reaction was stirred for an additional 10 <n="108"/>minutes and then poured into water. The mixture was then filtered, washed with DCM, washed with 10:1 DCMMeOH and dried to give N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-6- methylnicotinamide (260 g, 68.5% yield) as a solid

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 106-107

8
[ 1172068-36-8 ]
[ 100683-08-7 ]
[ 1196509-34-8 ]

Yield	Reaction Conditions	Operation in experiment
60%	With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine In dichloromethane at 20℃;	76.B 00513] Step B: Triethylamine (550 mg, 0.757 mL, 5.43 mmol) was slowly added to a mixture of 5-bromo-4-fluoro-lH-indol-3-amine (250 mg, 1.087 mmol, Example 1, step H), 1- methylcyclopropanecarboxylic acid (151 mg, 1.30 mmol) and bis(2-oxooxazolidin-3- yl)phosphinic chloride (415 mg, 1.63 mmol) in anhydrous dichloromethane (10 mL). The resulting solution was stirred at room temperature for 3 hours. The mixture was concentrated, and the residue purified by reverse phase chromatography (Biotage SP4 C- 18 25M column, 10- 75% CH3CN/water, 25CV) to give N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-l- methoxycyclopropanecarboxamide (216.5 mg, 60%) as a solid. 1H NMR (400 MHz, (CD3)2SO) δ 12.04 (br s, IH), 9,57 (s, IH), 8.36 (d, IH), 7.54 (d, IH), 3.39 (s, 3H), 1.16-1.11 (m, 4H). LCMS (APCI+) m/z 327.9 (M+H)+, Retention time = 2.96 minutes.

Reference： [1]Current Patent Assignee: PFIZER INC - WO2009/140320, 2009, A1 Location in patent: Page/Page column 166

9
[ 1172068-36-8 ]
[ 39901-94-5 ]
[ 1196509-18-8 ]

Yield	Reaction Conditions	Operation in experiment
82%		[00495] Step A: Picolinoyl chloride hydrochloride (501 mg, 2.82 mmol) was added to a solution of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (324 mg, 1.41 mmol, Example 1, Step H) in pyridine (5 mL). The reaction was stirred at room temperature for 10 minutes, and the pyridine was removed in vacuo. The residue obtained was dissolved in THF (5 mL), treated with 2N LiOH (3 mL), and stirred for 20 minutes. THF was then removed in vacuo, and water (20 mL) was added. The solid formed was collected by filtration and dried to provide N-(5- bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)picolinamide (389 mg, 82percent yield) as a solid. 1H NMR (400 MHz, (CD3^SO) delta 12.17 (br s, IH), 10.39 (s, IH), 8.76 (d, IH), 8.40 (d, IH), 8.17-8.15 (m, IH), 8.09 (dt, IH), 7.87 (d, IH), 7.71-7.68 (m, IH).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 158

10
[ 1172068-36-8 ]
[ 879-65-2 ]
[ 1196508-64-1 ]

Yield	Reaction Conditions	Operation in experiment
89%		[00443] Step A: 5-Bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (0.160 g, 0.696 mmol, Example 1, Step H), <strong>[879-65-2]quinoxaline-2-carboxylic acid</strong> (0.254 g, 1.46 mmol), BOP-Cl (0.372 g, 1.46 mmol), and triethylamine (0.352 g, 3.48 mmol) were placed in DCM (5 mL) at room temperature and stirred for 15 hours. 3M aqueous LiOH (3 mL) was then added, and the reaction was stirred for 10 minutes. Water (10 mL) and DCM (10 mL) were then added, and the reaction was filtered. The resulting solid was slurried with 10:1 DCM:MeOH and filtered to give solid N- (5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)quinoxaline-2-carboxamide (0.240 g, 89% yield).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 138

11
[ 1172068-36-8 ]
[ 25016-20-0 ]
[ 1196508-59-4 ]

Yield	Reaction Conditions	Operation in experiment
66%		[00430] Step A: TEA (1.21 niL, 8.69 mmol) was added to 5-bromo-4-fluoro-lH- pyrrolo[2,3-b]pyridin-3-amine (400 mg, 1.74 mmol, Example 1, Step H), 1 -methyl- lH-pyrazole- 3-carboxylic acid (260 mg, 2.09 mmol) and BOP-Cl (60 mg, 2.61 mmol) in DCM (5 mL). The reaction was stirred at room temperature for 1 hour, and then a LiOH solution (3 mL, 2N) was added. The mixture was stirred for 30 minutes, and water (10 mL) was added. The solid formed was collected by filtration, washed with DCM (5 mL) and dried to give N-(5-bromo-4-fluoro-lH- pyrrolo[2,3-b]pyridin-3-yl)-l-methyl-lH-pyrazole-3-carboxamide (30 mg, 66% yield) as a solid.

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 133

12
[ 1172068-36-8 ]
[ 277756-46-4 ]
[ 1196508-34-5 ]

Yield	Reaction Conditions	Operation in experiment
72%		00412] Step A: A solution of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H) in CH2CL (10 mL) was treated with <n="127"/>l-(trifluoromethyl)cyclopropanecarboxylic acid (161 mg, 1.04 mmol), bis(2-oxooxazolidin-3- yl)phosphinic chloride (332 mg, 1.30 mmol) and triethylamine (440 mg, 4.35 mmol). The reaction was stirred at room temperature for 1 hour. The mixture was concentrated in vacuo. The residue was stirred in anhydrous THF (10 mL), treated with 2M LiOH solution (3 mL) and stirred at room temperature for 1 hour. The organic solvent was removed in vacuo, and then water (10 mL) was added. The reaction was stirred for 1 hour. The solid, which separated, was filtered and washed with water and CH2CL (10 mL). The filtered cake was dried to yield N-(5- bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-l-(trifluoromethyl)cyclopropanecarboxamide (229.5 mg, 72% yield). 1H NMR (400 MHz, (CD3^SO) delta 12.15 (br s, IH), 9.38 (s, IH), 8.36 (d,IH), 7.51 (s, IH), 1.49-1.43 (m, 2H), 1.38-1.33 (m, 2H); LCMS (APCI+) m/z 366, 368 (M+H)+, Retention time = 3.32 minutes (Method 3).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 125-126

13
[ 23953-00-6 ]
[ 1172068-36-8 ]
[ 1196508-12-9 ]

Yield	Reaction Conditions	Operation in experiment
48%		00391] Step A: <strong>[23953-00-6](S)-2-Methoxypropanoic acid</strong> (181 mg, 1.74 mmol), bis(2-oxooxazolidin-3-yl)phosphinic chloride (443 mg, 1.74 mmol) and triethylamine (440 mg, 4.35 mmol) were added to 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.87 mmol, Example 1, Step H) in DCM (50 mL). The reaction was stirred at room temperature for 1 hour, and then 3M aqueous LiOH (4 mL) was added. The reaction was stirred for 1 hour, and then saturated aqueous Na2CO3 was added (200 mL). The aqueous phase was extracted 3 times with DCM(200 mL), and then the combined organic phases were dried over MgSO4 and concentrated to dryness. The residue was purified by C- 18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 20-100% CH3CN/water gradient; 20 CV) to yield (S)-N-(5-bromo-4- fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide (131mg, 48% yield) as a solid.

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 118

14
[ 1172068-36-8 ]
[ 5239-82-7 ]
[ 1196508-88-9 ]

Yield	Reaction Conditions	Operation in experiment
75%		00463] Step A: A mixture of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H), 2-<strong>[5239-82-7]cyclopropylacetic acid</strong> (218 mg, 2.17 mmol), triethylamine (606 muL, 4.35 mmol), and BOP-Cl (203 mg, 2.17 mmol) in CH2Cl2 (10 mL) was stirred at room temperature for 42 hours. Then 2M LiOH-H9O (3 mL) was added, and the mixture was stirred for 18 hours. The mixture was then diluted with CH2CL (50 mL). The layers were separated, and the organic layer was dried (MgSO4), filtered, and concentrated in vacuo to provide N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-2-cyclopropylacetamide (204 mg, 75% yield) as a solid. 1H NMR (400 MHz, (CD3)2SO) delta 12.04 (s, IH), 9.40 (s, IH),8.34 (d, IH), 7.61 (s, IH), 2.24 (d, 2H), 1.10-1.03 (m, IH), 0.52-0.47 (m, 2H), 0.24-0.20 (m, IH); LCMS (APCI+) m/z (M+H)+, Retention time = 2.92 minutes (Method 2).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 147

15
[ 31519-62-7 ]
[ 1172068-36-8 ]
[ 1196508-29-8 ]

Yield	Reaction Conditions	Operation in experiment
38%	With bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; triethylamine; In dichloromethane; at 20℃; for 48h;	[00406] Step A: A solution of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H) in CH2CL (10 mL) was treated with pyrimidine-2- carboxylic acid (129 mg, 1.04 mmol), bis(2-oxooxazolidin-3-yl)phosphinic chloride (332 mg, 1.30 mmol) and triethylamine (440 mg, 4.35 mmol). The reaction was stirred at room temperature for 48 hour, and then water (10 mL) was added. The reaction was stirred for 1 hour. The solid which separated was filtered and washed with CH9CL (10 mL). The filtered cake was dried to yield N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)pyrimidine-2-carboxamide (110 mg, 38% yield). 1H NMR (400 MHz, (CD3^SO) delta 12.21 (br s, IH), 10.47 (s, IH), 9.06 (d,2H), 8.40 (d, IH), 7 87 (d, IH), 7.77 (t, IH); LCMS (APCI+) m/z 335.9, 337.9 (M+H)+, Retention time = 2.70 minutes (Method 2).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 123

16
[ 1172068-36-8 ]
[ 80194-69-0 ]
[ 1196508-57-2 ]

Yield	Reaction Conditions	Operation in experiment
55%		[00426] Step A: TEA (0.61 niL, 4.35 mmol) was added to 5-bromo-4-fluoro-lH- pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.87 mmol, Example 1, Step H), 5- (trifluoromethyl)picolinic acid (200 mg, 1.04 mmol) and BOP-Cl (330 mg, 1.30 mmol) in DCM (5 mL). The reaction was stirred at room temperature for 1 hour, and then a LiOH solution (3 mL, 2N) was added. The mixture was stirred for 30 minutes, and water (10 mL) was added. The solid formed was collected by filtration, washed with DCM (10 mL) and dried to give N-(5- bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-5-(trifluoromethyl)picolinamide (195 mg, 55% yield) as a solid.

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 131

17
[ 1172068-36-8 ]
[ 26893-73-2 ]
[ 1196508-25-4 ]

Yield	Reaction Conditions	Operation in experiment
72%		[00403] Step A: A solution of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H) in CH2CL (10 mL) was treated with <strong>[26893-73-2]6-methoxypicolinic acid</strong> (160 mg, 1.04 mmol), bis(2-oxooxazolidin-3-yl)phosphinic chloride (332 mg, 1.30 mmol) and triethylamine (440 mg, 4.35 mmol). The reaction was stirred at room temperature for 1 hour, and then 2M aqueous LiOH (3 mL) was added. The reaction was stirred for 1 hour, and then water was added (10 mL). The solid, which separated, was filtered and washed with CH2CL (10 mL). The filtered cake was dried to yield N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)- 6-methoxypicolinamide (229 mg, 72% yield). 1H NMR (400 MHz, (CD3^SO) delta 12.17 (s, IH),12.25 (s, IH), 8.40 (d, IH), 7 96 (dd, IH), 7.92 (dd. IH), 7.74 (dd. IH), 7.11 (dd, IH), 4.05 (s, 3H); LCMS (APCI+) m/z 365, 366.9 (M+H)+, Retention time = 3.75 minutes (Method 2).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 122

18
[ 3719-45-7 ]
[ 1172068-36-8 ]
[ 1196507-90-0 ]

Yield	Reaction Conditions	Operation in experiment
69%		[00370] Step A: TEA (0.61 niL, 4.35 mmol) was added to 5-bromo-4-fluoro-lH- pyrrolo[2,3-b]pyridin-3-amine (0.20 g, 0.87 mmol, Example 1, Step H), l-methyl-6-oxo-l,6- dihydropyridine-3-carboxylic acid (0.17 g, 1.13 mmol) and BOP-Cl (0.33 g, 1.30 mmol) in DCM (10 mL). The reaction was stirred at room temperature for 1 hour, and then a LiOH solution (3 mL, 2N) was added. The mixture was stirred for 30 minutes, and water (10 mL) was added. The solid formed was collected by filtration, washed with DCM (10 mL) and dried to give N-(5- bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-l-methyl-6-oxo-l,6-dihydropyridine-3- carboxamide (0.22 g, 69percent yield) as a solid.

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 110

19
[ 23012-17-1 ]
[ 1172068-36-8 ]
[ 1196508-93-6 ]

Yield	Reaction Conditions	Operation in experiment
56%		[00469] Step A: A mixture of 5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-amine (200 mg, 0.869 mmol, Example 1, Step H), <strong>[23012-17-1]2-methyloxazole-4-carboxylic acid</strong> (276 mg, 2.17 mmol), <n="151"/>triethylamine (606 muL, 4.35 mmol), and BOP-Cl (203 mg, 2.17 mmol) in CH2Cl2 (10 niL) was stirred at room temperature for 4 hours. Next, 2M LiOH-H2O (3 mL) was added, and after 30 minutes water (10 mL) was added. The solid formed was filtered, washed with water (2 X 5 mL) and dried to provide N-(5-bromo-4-fluoro-lH-pyrrolo[2,3-b]pyridin-3-yl)-2-methyloxazole-4- carboxamide (165 mg, 56% yield) as a solid. chiH NMR (400 MHz, (CD3)2SO) delta 12.15 (s, IH),9.68 (s, IH), 8.63 (s, IH), 8.37 (d, IH), 7.67 (s, IH), 2.52 (s, 3H); LCMS (APCI+) m/z 338.9, 341.0(M+H)+, Retention time = 3.21 minutes (Method 2).

Reference： [1]Patent: WO2009/140320,2009,A1 .Location in patent: Page/Page column 149-150

20
[ 640735-25-7 ]
[ 1172068-36-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1 h / -78 °C 1.2: 1 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / 0.5 h / 0 °C 4.1: tin(II) chloride dihdyrate; hydrogenchloride / water / 1 h / 0 - 20 °C
	Multi-step reaction with 4 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / 1 h / -78 °C 1.2: 1 h / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / water / 0.5 h / 0 °C 4.1: tin(II) chloride dihdyrate; hydrogenchloride / water / 1 h / 0 - 20 °C
	Multi-step reaction with 4 steps 1.1: sec.-butyllithium / tetrahydrofuran; cyclohexane / -78 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 0.33 h / 20 °C 3.1: nitric acid / 0.5 h / 0 °C 4.1: hydrogenchloride; tin(ll) chloride / 0 - 20 °C 4.2: pH 7

Reference： [1]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - WO2013/114113, 2013, A1
[2]Current Patent Assignee: LIGAND PHARMACEUTICALS INC - US2015/11533, 2015, A1
[3]Current Patent Assignee: PFIZER INC - WO2009/140320, 2009, A1

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[ CAS No. 1172068-36-8 ] {[proInfo.proName]}

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[ 1172068-36-8 ] Synthesis Path-Downstream 1~20

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