Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][NH:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][CH:5]=1.S(Cl)([Cl:16])=O>>[CH3:1][N:2]=[C:3]([Cl:16])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][CH:5]=1
Reactant: O=S(Cl)Cl
Reactant: CNC(=O)c1ccc([N+](=O)[O-])cc1
Product: CN=C(Cl)c1ccc([N+](=O)[O-])cc1
Yield: 25.9 %

Procedure:
N-Methyl 4-nitrobenzamide (30.0 g, 167 mmole) and thionyl chloride (256 g, 2.15 mole) were heated at reflux for five hours. The excess thionyl chloride was removed at ~15 mm Hg. Xylene was added to the reaction and distilled under reduced pressure to yield a solid which was recrystallized from petroleum ether to yield 8.6 g of the title compound as a light yellow solid, m.p. 67°-73° C.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][N:5]2[C:8]([C:11]([NH:13][C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH3:33])=[N:17][N:18]4[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]([CH3:32])[CH3:31])[N:25]=3)=[O:12])=[CH:9][N:10]=[C:4]2[CH:3]=1.[CH3:34][C@@H:35]1[N:40]([CH3:41])[CH2:39][CH2:38][N:37]([CH2:42][CH2:43][OH:44])[CH2:36]1.O1CCN(CCO)C[CH2:46]1>>[CH:30]1([C:26]2[N:25]=[C:24]([CH2:23][N:18]3[C:19]4[C:15](=[C:14]([NH:13][C:11]([C:8]5[N:5]6[CH:6]=[CH:7][C:2]([O:44][CH2:43][CH2:42][N:37]7[CH2:38][CH2:39][N:40]([CH3:41])[C@@H:35]([CH3:34])[CH2:36]7)=[CH:3][C:4]6=[N:10][CH:9]=5)=[O:12])[CH:22]=[CH:21][CH:20]=4)[C:16]([CH3:33])=[N:17]3)[CH:29]=[CH:28][CH:27]=2)[CH2:32][CH2:46][CH2:31]1
Reactant: OCCN1CCOCC1
Reactant: Cc1nn(Cc2cccc(C(C)C)n2)c2cccc(NC(=O)c3cnc4cc(F)ccn34)c12
Reactant: C[C@H]1CN(CCO)CCN1C
Product: Cc1nn(Cc2cccc(C3CCC3)n2)c2cccc(NC(=O)c3cnc4cc(OCCN5CCN(C)[C@@H](C)C5)ccn34)c12
Yield: 29 %

Procedure:
Prepared according Example 1, Step B, substituting N-(1-((6-cyclobutylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)-7-fluoroimidazo[1,2-a]pyridine-3-carboxamide for 7-fluoro-N-(1-((6-isopropylpyridin-2-yl)methyl)-3-methyl-1H-indazol-4-yl)imidazo[1,2-a]pyridine-3-carboxamide and (S)-2-(3,4-dimethylpiperazin-1-yl)ethanol for 2-morpholinoethanol to give the title compound (29%). MS (APCI), positive scan, m/z=593.1 (M+H).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1[C:11]([CH:12]=[CH2:13])=[C:10]([S:14][CH3:15])[N:9]=[C:8]([NH2:16])[N:7]=1.[H][H]>C(O)C.[Pd]>[CH2:12]([C:11]1[C:6]([C:2]2[O:1][CH:5]=[CH:4][CH:3]=2)=[N:7][C:8]([NH2:16])=[N:9][C:10]=1[S:14][CH3:15])[CH3:13]
Reactant: [H][H]
Reactant: C=Cc1c(SC)nc(N)nc1-c1ccco1
Agent: [Pd]
Solvent: CCO
Product: CCc1c(SC)nc(N)nc1-c1ccco1
Yield: 29.6 %

Procedure:
A solution of 200 mg (0.86 mmol) 4-furan-2-yl-6-methylsulfanyl-5-vinyl-pyrimidin-2-ylamine in 30 ml ethanol was stirred with a spatula end of 10% palladium on charcoal under 1 atm of hydrogen for 16 h at room temperature. After filtration to remove the catalyst, the reaction mixture was concentrated in vacuo and the residue triturated in ether/hexane to afford 60 mg (30%) 5-ethyl-4-furan-2-yl-6-methylsulfanyl-pyrimidin-2-ylamine as an off-white crystalline solid. ES-MS rn/e (%): 236 (M+H+, 100).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][S:6][C:7]1[CH:8]=[C:9]([O:17]COC)[C:10]([O:13]COC)=[N:11][CH:12]=1.Cl>O1CCOCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:21]=[CH:22][CH:23]=1)[CH2:5][S:6][C:7]1[CH:8]=[C:9]([OH:17])[C:10](=[O:13])[NH:11][CH:12]=1
Reactant: COCOc1cc(SCc2cccc(F)c2)cnc1OCOC
Agent: Cl
Solvent: C1COCCO1
Product: O=c1[nH]cc(SCc2cccc(F)c2)cc1O
Reaction time: 16 h
Yield: 60.6 %

Procedure:
To a solution of 5-[(3-fluorobenzyl)sulfanyl]-2,3-bis(methoxymethoxy)pyridine (Intermediate 43; 690 mg, 2.03 mmol) in dioxane (4 ml) was added a solution of hydrogen chloride in dioxane (4.0 M; 2.54 ml, 10.17 mmol) and the reaction stirred for 16 hours before being concentrated in vacuo. The crude product was recrystallised from ethanol and water to yield 5-[(3-fluorobenzyl)sulfanyl]-3-hydroxypyridin-2(1H)-one as a pale grey solid (309 mg, 61%).
Reaction SMILES: [H-].[Na+].[CH3:3][CH:4]([CH3:7])[CH2:5][OH:6].[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:22]=[N:23][C:24]([NH:27][C:28]3[N:29]=[CH:30][C:31]4[CH:37]=[C:36](F)[C:35](=[O:39])[N:34]([CH:40]5[CH2:44][CH2:43][CH2:42][CH2:41]5)[C:32]=4[N:33]=3)=[CH:25][CH:26]=2)[CH2:17][CH2:16]1)=[O:14])([CH3:11])([CH3:10])[CH3:9]>CCCCCC>[C:8]([O:12][C:13]([N:15]1[CH2:16][CH2:17][N:18]([C:21]2[CH:22]=[N:23][C:24]([NH:27][C:28]3[N:29]=[CH:30][C:31]4[CH:37]=[C:36]([O:6][CH2:5][CH:4]([CH3:7])[CH3:3])[C:35](=[O:39])[N:34]([CH:40]5[CH2:41][CH2:42][CH2:43][CH2:44]5)[C:32]=4[N:33]=3)=[CH:25][CH:26]=2)[CH2:19][CH2:20]1)=[O:14])([CH3:11])([CH3:9])[CH3:10]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(Nc3ncc4cc(F)c(=O)n(C5CCCC5)c4n3)nc2)CC1
Reactant: CC(C)CO
Agent: [H-]
Agent: [Na+]
Solvent: CCCCCC
Product: CC(C)COc1cc2cnc(Nc3ccc(N4CCN(C(=O)OC(C)(C)C)CC4)cn3)nc2n(C2CCCC2)c1=O
Temperature: 95 °C
Yield: 37 %

Procedure:
60% Sodium hydride in oil (0.182 g, 4.4 mmol) was washed with hexane and added to 2-methyl-1-propanol (10 ml). This mixture effervesced and formed a solution. To this solution was added 4-[6-(8-cyclopentyl-6-fluoro-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (0.225 g, 0.44 mmol, prepared as in Example 17) and the mixture was heated at 95° C. for 72 hours. The solvents were evaporated, and the residue was dissolved in diethyl ether then filtered. The filtrate was evaporated to provide 4-[6-(8-cyclopentyl-6-isobutoxy-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester as a crystalline solid (0.092 g, 37%). MS (APCI) M++1: Calc'd, 564.3. Found 564.3.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[C:11]([CH:32]=[CH:33][CH:34]=2)[C:12]([NH:14][C:15]2[CH:16]=[C:17]([NH:22][C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27](Cl)[N:26]=3)=[O:24])[CH:18]=[CH:19][C:20]=2[CH3:21])=[O:13])[CH2:4][CH2:3]1.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>O>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:10]=[C:11]([CH:32]=[CH:33][CH:34]=2)[C:12]([NH:14][C:15]2[CH:16]=[C:17]([NH:22][C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([N:35]4[CH2:40][CH2:39][O:38][CH2:37][CH2:36]4)[N:26]=3)=[O:24])[CH:18]=[CH:19][C:20]=2[CH3:21])=[O:13])[CH2:4][CH2:3]1
Reactant: C1COCCN1
Reactant: Cc1ccc(NC(=O)c2cccc(Cl)n2)cc1NC(=O)c1cccc(CN2CCN(C)CC2)c1
Solvent: O
Product: Cc1ccc(NC(=O)c2cccc(N3CCOCC3)n2)cc1NC(=O)c1cccc(CN2CCN(C)CC2)c1
Temperature: 110 °C

Procedure:
A mixture of N-{3-[3-(4-methylpiperazin-1-ylmethyl)benzamido]-4-methylphenyl}-6-chloropyridine-2-carboxamide (0.2 g) and morpholine (3 ml) was stirred and heated to 110° C. for 16 hours. The resultant solution was cooled to ambient temperature and poured into water and extracted with methylene chloride. The organic phase was evaporated and the residue was purified by reversed-phase column chromatography on a C18 isolute column eluting initially with water and then with a 5:1 mixture of water and methanol. There was thus obtained the title compound (0.169 g); NMR Spectrum: (DMSOd6) 2.15 (s, 3H), 2.19 (s, 3H), 2.25-2.39 (m, 8H), 3.52 (s, 2H), 3.57-3.6 (m, 4H), 3.71-3.75 (m, 4H), 7.05 (d, 1H), 7.22 (d, 1H), 7.4-7.49 (m, 3H), 7.64 (d, 1H), 7.76 (t, 1H), 7.82-7.88 (m, 3H), 9.92 (s, 1H), 10.08 (s, 1H); Mass Spectrum: M+H+ 529.
Reaction SMILES: [Cl:1][C:2]1[C:3]([S:8][C:9]2[CH:16]=[CH:15][C:12]([CH2:13][OH:14])=[CH:11][C:10]=2[N+:17]([O-])=O)=[N:4][CH:5]=[CH:6][N:7]=1.[Cl-].[NH4+]>O1CCCC1.CC(O)C.O.[Fe]>[NH2:17][C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][C:9]=1[S:8][C:3]1[C:2]([Cl:1])=[N:7][CH:6]=[CH:5][N:4]=1)[CH2:13][OH:14]
Reactant: O=[N+]([O-])c1cc(CO)ccc1Sc1nccnc1Cl
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CC(C)O
Solvent: C1CCOC1
Solvent: O
Product: Nc1cc(CO)ccc1Sc1nccnc1Cl
Yield: 102.2 %

Procedure:
1.60 g of 4-[(3-chloropyrazin-2-yl)thio]-3-nitrobenzyl alcohol was dissolved in a solvent mixture of tetrahydrofuran (20 ml)/2-propanol (20 ml)/water (7 ml). After adding 0.16 g of ammonium chloride and 1.50 g of iron powder, the resulting mixture was heated under reflux for 30 minutes. Then the reaction mixture was filtered through celite and concentrated under reduced pressure. After adding ethanol, the reaction mixture was concentrated under reduced pressure. Then tetrahydrofuran was added to the residue and the insoluble matters were separated by filtration. After distilling off the solvent under reduced pressure, 1.47 g of the title compound was obtained as yellow crystals.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=2)[NH:4][N:3]=1.C(OC(=O)C)C.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1>>[N:20]1([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([N+:11]([O-:13])=[O:12])[CH:9]=3)[NH:4][N:3]=2)[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1
Reactant: O=[N+]([O-])c1ccc2[nH]nc(Br)c2c1
Reactant: C1COCCN1
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1ccc2[nH]nc(N3CCOCC3)c2c1

Procedure:
3-Bromo-5-nitro-1H-indazole (0.5 gm, 2 mmol) was dissolved in 3.5 ml of morpholine and heated in a sealed tube for 40 hrs. The mixture was then cooled and added to ethylacetate, washed with brine and dried over magnesium sulfate. After chromatography on silica gel using 20-50% ethylacetate/hexanes as eluent the title compound was obtained (210 mg, 0.85 mmol).
Reaction SMILES: [C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]1[CH2:11][C@H:10]([NH:12][C:13]2[C:18]([NH2:19])=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[C:21](OC)(OC)(OC)[O:22][CH3:23].C(O)(=O)CC>O>[C:1]([O:5][C:6](=[O:20])[NH:7][C@H:8]1[CH2:11][C@H:10]([N:12]2[C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:18]3[N:19]=[C:21]2[O:22][CH3:23])[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@H]1C[C@H](Nc2ncccc2N)C1
Reactant: COC(OC)(OC)OC
Solvent: O
Solvent: CCC(=O)O
Product: COc1nc2cccnc2n1[C@H]1C[C@H](NC(=O)OC(C)(C)C)C1
Temperature: 100 °C

Procedure:
To a glass microwave vial was added tert-butyl(trans-3-((3-aminopyridin-2-yl)amino)cyclobutyl)carbamate (intermediate 12, step 2, 1.7367 g, 6.24 mmol), tetramethyl orthocarbonate (16.66 ml, 125 mmol), and propionic acid (0.233 ml, 3.12 mmol). The reaction mixture was heated at 100° C. for 5 hours then was allowed to cool to room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water, brine, and dried over magnesium sulfate before evaporating to dryness under reduced pressure. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP HP-silica gel column (50 g), eluting with a gradient of 10% to 100% ethyl acetate in hexane, to provide tert-butyl(trans-3-(2-methoxy-3H-imidazo[4,5-b]pyridin-3-yl)cyclobutyl)carbamate (0.968 g, 3.04 mmol, 48.7% yield).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([CH2:10][CH2:11][CH2:12][NH:13][CH2:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=2)=[CH:8][CH:9]=1)=[O:4].[CH:24]1([S:27](Cl)(=[O:29])=[O:28])[CH2:26][CH2:25]1.C(N(CC)CC)C>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([CH2:10][CH2:11][CH2:12][N:13]([CH2:14][CH2:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[CH:18]=2)[S:27]([CH:24]2[CH2:26][CH2:25]2)(=[O:29])=[O:28])=[CH:8][CH:9]=1)=[O:4]
Reactant: COC(=O)c1ccc(CCCNCCCc2cccc(Cl)c2)s1
Reactant: O=S(=O)(Cl)C1CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)c1ccc(CCCN(CCCc2cccc(Cl)c2)S(=O)(=O)C2CC2)s1
Temperature: 25 °C
Reaction time: 48 h
Yield: 117.1 %

Procedure:
To a solution of 5-{3-[3-(3-chloro-phenyl)-propylamino]-propyl}-thiophene-2-carboxylic acid methyl ester (51.5 mg, 0.1463 mmol), of Preparation 8, in CH2Cl2 (10 mL) at 0° C. was added cyclopropanesulfonyl chloride (22.6 mg, 0.161 mmol) and triethylamine (0.45 mL, 0.32 mmol). The reaction was warmed to room temperature and was stirred for 48 h. The reaction was heated at reflux for 48 h and additional triethylamine (0.45 mL) and cyclopropanesulfonyl chloride (22.6 mg) were added. The reaction was heated at reflux for 7.5 h, was cooled to room temperature and was stirred for 72 h. The reaction was heated at reflux for 24 h. The organic solution was washed sequentially with 5.5% aqueous HCl, water, saturated sodium bicarbonate solution, and brine. The organic solution was dried (MgSO4), filtered, and concentrated to provide the title compound of Step A (78.1 mg). MS 456 (M+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:12])=[C:6]([CH2:8][C:9]([OH:11])=O)[CH:7]=1.S(Cl)(Cl)=O.Cl.[NH2:18][C:19]1([C:25]([O:27][CH3:28])=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:12])=[C:6]([CH2:8][C:9]([NH:18][C:19]2([C:25]([O:27][CH3:28])=[O:26])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:11])[CH:7]=1
Reactant: COC(=O)C1(N)CCCCC1
Reactant: Cc1ccc(Br)cc1CC(=O)O
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)C1(NC(=O)Cc2cc(Br)ccc2C)CCCCC1
Temperature: 80 °C
Reaction time: 2 h

Procedure:
2.06 g (9.00 mmol) of (5-bromo-2-methylphenyl)acetic acid (described in EP 1791816 and WO 2006/29799) were dissolved in 3.7 ml (51.3 mmol) of thionyl chloride. The reaction mixture was stirred at 80° C. for 2 h and then concentrated. The residue was dissolved in 20 ml of dichloromethane. 2.09 g (10.8 mmol) of methyl 1-aminocyclohexanecarboxylate hydrochloride were dissolved in 25 ml of dichloromethane, 55 mg (0.45 mmol) of 4-dimethylaminopyridine and 3.1 ml (22.5 mmol) of triethylamine were added and the mixture was stirred at room temperature for 0.5 h. The solution of the acid chloride was added dropwise, and the mixture was stirred at room temperature for 36 h. The mixture was then diluted with diluted with dichloromethane, washed with water, 1N aqueous hydrogen chloride solution and saturated aqueous sodium bicarbonate solution, dried, filtered and concentrated. This gave 2.80 g (84% of theory) of the title compound.
Reaction SMILES: [NH2:1][C:2]([C:4]1[S:5][C:6]([N:32]2[C:36]3[CH:37]=[CH:38][C:39]([C:41]4[CH:42]=[N:43][N:44]([CH3:46])[CH:45]=4)=[CH:40][C:35]=3[N:34]=[CH:33]2)=[CH:7][C:8]=1[O:9][CH:10]([C:12]1[CH:13]=[C:14]([O:18][CH:19]2[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]2)[CH:15]=[CH:16][CH:17]=1)[CH3:11])=[O:3].C(O)(C(F)(F)F)=O.[OH-].[Na+]>C(Cl)Cl>[CH3:46][N:44]1[CH:45]=[C:41]([C:39]2[CH:38]=[CH:37][C:36]3[N:32]([C:6]4[S:5][C:4]([C:2]([NH2:1])=[O:3])=[C:8]([O:9][CH:10]([C:12]5[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH:19]6[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]6)[CH:13]=5)[CH3:11])[CH:7]=4)[CH:33]=[N:34][C:35]=3[CH:40]=2)[CH:42]=[N:43]1
Reactant: CC(Oc1cc(-n2cnc3cc(-c4cnn(C)c4)ccc32)sc1C(N)=O)c1cccc(OC2CCN(C(=O)OC(C)(C)C)CC2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(Oc1cc(-n2cnc3cc(-c4cnn(C)c4)ccc32)sc1C(N)=O)c1cccc(OC2CCNCC2)c1
Temperature: 0 °C
Yield: 68.3 %

Procedure:
(+/−)-1,1-Dimethylethyl 4-({3-[1-({2-(aminocarbonyl)-5-[5-(1-methyl-1H-pyrazol-4-yl)-1H-benzimidazol-1-yl]-3-thienyl}oxy)ethyl]phenyl}oxy)-1-piperidinecarboxylate (0.378 g, 0.588 mmol) was dissolved in 12 mL of DCM with stirring and cooled to 0° C. TFA (3.0 mL, 39 mmol) was added, and the reaction was stirred for 1.5 h. The reaction was pipeted onto 80 mL of aqueous 2N NaOH solution, rinsing with DCM. The mixture was extracted three times with 4:1 DCM/i-PrOH. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography afforded 0.218 g (68%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.51 (s, 1H), 8.17 (s, 1H), 7.93 (m, 1H), 7.90 (s, 1H), 7.75 (br s, 1H), 7.55 (dd, J=8.4, 1.4 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.42 (s, 1H), 7.26 (dd, J=8.1, 7.9 Hz, 1H), 7.11-7.06 (m, 2H), 7.04 (d, J=7.9 Hz, 1H), 6.84 (dd, J=8.1, 2.2 Hz, 1H), 5.69 (q, J=6.4 Hz, 1H), 4.34 (m, 1H), 3.84 (s, 3H), 2.90-2.81 (m, 2H), 2.53-2.43 (m, 2H), 1.88-1.76 (m, 2H), 1.67 (d, J=6.4 Hz, 3H), 1.42-1.26 (m, 2H). MS (APCI): 543 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[C:13]([CH3:14])=[CH:12][C:5]2[CH2:6][C:7](=[O:11])[NH:8][CH:9]=[CH:10][C:4]=2[CH:3]=1.Br[CH2:16][CH2:17][CH2:18][Cl:19]>>[CH3:1][C:2]1[C:13]([CH3:14])=[CH:12][C:5]2[CH2:6][C:7](=[O:11])[N:8]([CH2:16][CH2:17][CH2:18][Cl:19])[CH:9]=[CH:10][C:4]=2[CH:3]=1
Reactant: Cc1cc2c(cc1C)CC(=O)NC=C2
Reactant: ClCCCBr
Product: Cc1cc2c(cc1C)CC(=O)N(CCCCl)C=C2

Procedure:
This compound was prepared analogous to Example 1(a) by reacting 7,8-dimethyl-1,3-dihydro-2H-3-benzazepin-2-one (m.p. 220°-224° C.) with 1-bromo-3-chloro-propane.
Reaction SMILES: [C:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)([OH:3])=[O:2].[CH3:12][C:13](=[O:18])[CH2:14][C:15](=[O:17])[CH3:16].S(Cl)(Cl)=O>CC(O)C>[C:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[C:14]([C:13](=[O:18])[CH3:12])[C:15](=[O:17])[CH3:16])=[CH:6][CH:5]=1)([OH:3])=[O:2]
Reactant: O=Cc1ccc(C(=O)O)cc1
Reactant: CC(=O)CC(C)=O
Solvent: CC(C)O
Solvent: O=S(Cl)Cl
Product: CC(=O)C(=Cc1ccc(C(=O)O)cc1)C(C)=O

Procedure:
To a suspension containing 3.0 g (0.02mol) of 4-carboxybenzaldehyde and 3.0 g (0.03mol) of 2,4-pentanedione in 10ml of 2-propanol was gradually added 3.0 g (0.025mol) of thionyl chloride with stirring and cooling (below 20° C). The mixture was stirred over night at 20° C. After filtering the product was washed with 2-propanol, yield 1.8 g, mp 195°-199° C.
Reaction SMILES: C(OC([N:8]1[CH2:12][C@@H:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[C:22]([OH:24])=[O:23])=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][O:13][C@@H:11]2[CH2:12][NH:8][C@H:9]([C:22]([OH:24])=[O:23])[CH2:10]2)=[CH:16][CH:17]=1
Reactant: CC(C)(C)OC(=O)N1C[C@@H](OCc2ccc(Cl)cc2)C[C@H]1C(=O)O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)[C@@H]1C[C@H](OCc2ccc(Cl)cc2)CN1
Reaction time: 8 h
Yield: 5.1 %

Procedure:
(2S,4S)-1-(tert-butoxycarbonyl)-4-[(4-chlorobenzyl)oxy]-2-pyrrolidinecarboxylic acid (Preparation 4, 96 mg, 0.38 mmol) was dissolved in dichloromethane (5 ml). Trifluoroacetic acid (5 ml) was added and the mixture left overnight at room temperature. The reaction mixture was partitioned between dichloromethane (25 ml) and water (25 ml). The aqueous layer was separated, washed with more dichloromethane (25 ml) and evaporated to dryness. The product was purified using Dowex™ 50WX8-200 resin, eluting first with water then 9:1 water:ammonia yielding the title compound (5 mg, 5% yield) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10]([N:12]2[CH:21]([CH3:22])[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13]2)[C:9]2[C:4](=[C:5]([O:23][CH3:24])[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[F:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[C:28]([CH3:33])[CH:27]=1>CN(C)C=O>[ClH:1].[F:25][C:26]1[CH:32]=[CH:31][C:29]([NH:30][C:2]2[N:11]=[C:10]([N:12]3[CH:21]([CH3:22])[CH2:20][C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH2:13]3)[C:9]3[C:4](=[C:5]([O:23][CH3:24])[CH:6]=[CH:7][CH:8]=3)[N:3]=2)=[C:28]([CH3:33])[CH:27]=1
Reactant: COc1cccc2c(N3Cc4ccccc4CC3C)nc(Cl)nc12
Reactant: Cc1cc(F)ccc1N
Solvent: CN(C)C=O
Product: COc1cccc2c(N3Cc4ccccc4CC3C)nc(Nc3ccc(F)cc3C)nc12
Product: Cl
Yield: 29 %

Procedure:
In accordance with the same procedures as in Example 18, except that to a mixture of 2.0 g of the compound (5.9 mM) prepared in Example 12 and 15 ml of dimethyl-formamide, 1.1 ml of 4-fluoro-2-methylaniline(8.9 mM) was added, 0.8 g of the title compound was prepared.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=2)[N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH:6]=1.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28](B(O)O)[CH:27]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:10]([O:9][C:7]([N:5]1[CH:6]=[C:2]([C:28]2[CH:27]=[N:26][CH:31]=[CH:30][CH:29]=2)[CH:3]=[C:4]1[C:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17]([O:22][CH3:23])=[C:16]([O:24][CH3:25])[CH:15]=1)=[O:8])([CH3:13])([CH3:12])[CH3:11]
Reactant: COc1cc(-c2cc(Br)cn2C(=O)OC(C)(C)C)cc(OC)c1OC
Reactant: OB(O)c1cccnc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: COc1cc(-c2cc(-c3cccnc3)cn2C(=O)OC(C)(C)C)cc(OC)c1OC
Temperature: 25 °C
Yield: 13.6 %

Procedure:
A mixture of 4-bromo-1-tert-butoxycarbonyl-2-(3,4,5-trimethoxyphenyl)-pyrrole (2.0 g, 5.0 mmol, Example 76b), Pd(PPh3)4 (290 mg, 0.25 mmol) and pyridine-3-boronic acid (614 mg, 5.0 mmol) are evacuated for 10 min and set under argon atmosphere, followed by addition of degassed dimethoxyethane (DME, 10 ml) and 2 M aqueous Na2CO3 solution (10 ml). The reaction mixture is heated for 20 h to 80° C., cooled to room temperature and diluted with water and ethyl acetate. The organic layer is dried (MgSO4), filtered and the solvents are evaporated. The residue is chromatographed with ethyl acetate/hexane (1:1) to yield first 1-tert-butoxycarbonyl-4-(3-pyridyl)-2-(3,4,5-trimethoxy-phenyl)-pyrrole (280 mg, 12%) as a yellowish amorphous solid and then the title compound (700 mg, 45%) as a yellowish solid, 1H-NMR (300 MHz, DMSO-d6): 11.52 (br.s, 1H); 7.88 (br. s, 1H); 8.33 (br.d; J=6.0, 1H); 8.0-7.95 (m, 1H); 7.48 (br.s, 1H); 7.35-7.3 (m, 1H); 7.07 (br.s, 1H); 7.02 (s, 2H); 3.85 (s, 2MeO); 3.67 (s, MeO).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2CC[C:8]3[C:13]([C:14]=2[CH:15]=1)=[CH:12][C:11]([Br:16])=[CH:10][CH:9]=3.Cl.C([O:21][CH2:22][CH3:23])(=O)C.C(OC(=O)C)(=[O:26])C>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:22](=[O:21])[C:23](=[O:26])[C:8]3[C:13]([C:14]=2[CH:15]=1)=[CH:12][C:11]([Br:16])=[CH:10][CH:9]=3
Reactant: Brc1ccc2c(c1)-c1cc(Br)ccc1CC2
Reactant: CCOC(C)=O
Reactant: CC(=O)OC(C)=O
Agent: Cl
Product: O=C1C(=O)c2ccc(Br)cc2-c2cc(Br)ccc21

Procedure:
The present invention provides a polymer applied to solar cell and its fabrication method thereof. The 3,6-dibromophenanthrene-9,10-dione is prepared by a suitable method firstly. In an embodiment, N-bromosuccinimide (NBS) is dropped into a solution composed of 9,10-dihydrophenanthrene, tetrahydrofuran (THF), and acetic acid gradually, and agitate the mixture for 20 minutes. Add the saturated NaHCO3, and use water to rinse the solution. Use ethyl acetate to extract the solution. Use MgSO4 to dry the organic layer, and concentrate it to obtain 3,6-dibromo-9,10-dihydrophenanthrene. Then dissolve 3,6-dibromo-9,10-dihydrophenanthrene and chromic trioxide in acetic anhydride, and react at room temperature for several hours. Pour the solution into 1N HCl solution. Use ethyl acetate to extract the solution. Use MgSO4 to dry the organic layer, and concentrate it to obtain 3,6-dibromophenanthrene-9,10-dione.
Reaction SMILES: Cl.Cl.[NH:3]1[CH2:8][CH2:7][CH:6]([N:9]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]2=[O:18])[CH2:5][CH2:4]1.CCN(C(C)C)C(C)C.Cl[C:29]1[N:34]=[CH:33][N:32]=[C:31]([C:35]([N:37]2[C:45]3[C:40](=[CH:41][C:42]([F:46])=[CH:43][CH:44]=3)[CH:39]=[CH:38]2)=[O:36])[CH:30]=1>CN(C=O)C>[F:46][C:42]1[CH:41]=[C:40]2[C:45](=[CH:44][CH:43]=1)[N:37]([C:35]([C:31]1[N:32]=[CH:33][N:34]=[C:29]([N:3]3[CH2:4][CH2:5][CH:6]([N:9]4[C:17]5[C:12](=[N:13][CH:14]=[CH:15][CH:16]=5)[NH:11][C:10]4=[O:18])[CH2:7][CH2:8]3)[CH:30]=1)=[O:36])[CH:38]=[CH:39]2
Reactant: O=c1[nH]c2ncccc2n1C1CCNCC1
Reactant: O=C(c1cc(Cl)ncn1)n1ccc2cc(F)ccc21
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(c1cc(N2CCC(n3c(=O)[nH]c4ncccc43)CC2)ncn1)n1ccc2cc(F)ccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
75.0 mg (0.26 mmol) 1-piperidin-4-yl-1,3-dihydro-imidazo[4,5-b]pyridin-2-one dihydrochloride and 150 μL (0.87 mmol) DIPEA were added to 70 mg (0.25 mmol) (6-chloropyrimidin-4-yl)-(5-fluoroindol-1-yl)-methanone in 5 mL DMF. The reaction mixture was stirred overnight at RT and then evaporated down i. vac. The residue was taken up in 20 mL water and stirred for 10 min. The precipitate was suction filtered, dissolved in 2.5 mL DMF and purified by preparative HPLC. The product fractions were combined and concentrated by rotary evaporation using the rotary evaporator.