Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[S:15][C:5]2[N:6]([CH3:14])[C:7]([C:9](OCC)=[O:10])=[CH:8][C:4]=2[CH:3]=1.CC(C[AlH]CC(C)C)C>C(Cl)Cl>[Br:1][C:2]1[S:15][C:5]2[N:6]([CH3:14])[C:7]([CH2:9][OH:10])=[CH:8][C:4]=2[CH:3]=1
Reactant: CCOC(=O)c1cc2cc(Br)sc2n1C
Agent: CC(C)C[AlH]CC(C)C
Solvent: ClCCl
Product: Cn1c(CO)cc2cc(Br)sc21
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 101.1 %

Procedure:
To solution of ethyl 2-bromo-6-methyl-6H-thieno[2,3-b]pyrrole-5-carboxylate (5.47 g, 18.28 mmol) in DCM (55 mL) at −78° C. was added solution of DIBAL-H (1M hexanes, 42.00 mL, 42.00 mmol). Reaction mixture was stirred 30 min at −78° C. before it was quenched with Na—K-tartrate (aqueous saturated, 50 mL). Mixture was allowed to warm to room temperature and was stirred 1 h. Product was extracted with DCM (3×100 mL). Organic phase was washed with NaCl (aqueous saturated, 50 mL) and dried over Na2SO4. Solvent was concentrated to yield (2-bromo-6-methyl-6H-thieno[2,3-b]pyrrol-5-yl)methanol (4.55 g, 97%) as solid which was used in the next step without purification.
Reaction SMILES: NC1C2=C(C3C=CC(NC(NC4C=C(C(F)(F)F)C=CC=4F)=O)=C(F)C=3)C=C(CCCBr)N2N=CN=1.O1CCCNCC1.[NH2:44][C:45]1[C:50]2=[C:51]([C:65]3[CH:70]=[CH:69][C:68]([NH:71][C:72]([NH:74][C:75]4[CH:80]=[C:79]([C:81]([F:84])([F:83])[F:82])[CH:78]=[CH:77][C:76]=4[F:85])=[O:73])=[C:67]([F:86])[CH:66]=3)[CH:52]=[C:53]([CH2:54][CH2:55][CH2:56][N:57]3[CH2:61][CH2:60]C[C@H:58]3[CH2:62][O:63][CH3:64])[N:49]2[N:48]=[CH:47][N:46]=1>>[NH2:44][C:45]1[C:50]2=[C:51]([C:65]3[CH:70]=[CH:69][C:68]([NH:71][C:72]([NH:74][C:75]4[CH:80]=[C:79]([C:81]([F:83])([F:82])[F:84])[CH:78]=[CH:77][C:76]=4[F:85])=[O:73])=[C:67]([F:86])[CH:66]=3)[CH:52]=[C:53]([CH2:54][CH2:55][CH2:56][N:57]3[CH2:61][CH2:60][CH2:64][O:63][CH2:62][CH2:58]3)[N:49]2[N:48]=[CH:47][N:46]=1
Reactant: COC[C@@H]1CCCN1CCCc1cc(-c2ccc(NC(=O)Nc3cc(C(F)(F)F)ccc3F)c(F)c2)c2c(N)ncnn12
Agent: C1CNCCOC1
Agent: Nc1ncnn2c(CCCBr)cc(-c3ccc(NC(=O)Nc4cc(C(F)(F)F)ccc4F)c(F)c3)c12
Product: Nc1ncnn2c(CCCN3CCCOCC3)cc(-c3ccc(NC(=O)Nc4cc(C(F)(F)F)ccc4F)c(F)c3)c12
Yield: 22 %

Procedure:
1-{4-[4-amino-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro -5-(trifluoromethyl)phenyl]urea (50 mg, 0.088 mmol) and 1,4-oxazepane (36 mg, 0.263 mmol) were allowed to react using the procedure to make N-[4-(4-amino-7-{3-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]propyl}pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea. The product was purified by column chromatography using a 4 g MPLC column. The eluent was 0-10.0% (2N NH3 in MeOH)/CH2Cl2 to yield clean product (11 mg, 22%) 1H-NMR (DMSO-d6) δ 9.41 (s, 1H), 9.25 (s, 1H), 8.66 (m, 1H), 8.26 (t, J=8.7 Hz, 1H), 7.89 (s, 1H), 7.52 to 7.22 (m, 4H), 6.58 (s, 1H), 3.66 to 3.56 (m, 4H), 2.90 to 2.42 (m, 8H), 2.57 (m, 2H), 1.79 (m, 4H), MS [M+H]+=590.2; LCMS RT=2.61
Reaction SMILES: [N:1]1([CH2:10][CH2:11][N:12]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH2:9][CH2:8][NH:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[C:27](Cl)([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[C:27]([N:7]1[CH2:8][CH2:9][N:1]([CH2:10][CH2:11][N:12]2[CH2:13][CH2:14][N:15]([C:27]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:16][CH2:17][N:18]([C:27]([C:34]3[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=3)([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:19][CH2:20]2)[CH2:2][CH2:3][N:4]([C:27]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH2:5][CH2:6]1)([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: C1CNCCN(CCN2CCNCCNCC2)CCN1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: c1ccc(C(c2ccccc2)(c2ccccc2)N2CCN(CCN3CCN(C(c4ccccc4)(c4ccccc4)c4ccccc4)CCN(C(c4ccccc4)(c4ccccc4)c4ccccc4)CC3)CCN(C(c3ccccc3)(c3ccccc3)c3ccccc3)CC2)cc1

Procedure:
From 1,2-Bis(1,4,7-triazacyclononane)ethane (1.1.28), potassium carbonate and trityl chloride.
Reaction SMILES: [Br:1][CH2:2][CH2:3]Br.C(=O)([O-])[O-].[K+].[K+].[Cl:11][C:12]1[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[CH:15]=[CH:14][C:13]=1[OH:21]>CN(C=O)C.C(OCC)(=O)C>[Br:1][CH2:2][CH2:3][O:21][C:13]1[CH:14]=[CH:15][C:16]([N+:18]([O-:20])=[O:19])=[CH:17][C:12]=1[Cl:11]
Reactant: BrCCBr
Reactant: O=[N+]([O-])c1ccc(O)c(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1ccc(OCCBr)c(Cl)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
36.6 mL (416 mmol) of 1,2-dibromoethane is dissolved in 200 mL of DMF and 11.5 g (83.3 mmol) of potassium carbonate is added. 7.20 g (41.6 mmol) of 2-chloro-4-nitrophenol in 40 mL of DMF is slowly added dropwise to this mixture. The mixture is stirred for 3 hours at ambient temperature. The solvent is eliminated, the residue is taken up in ethyl acetate and washed with saturated saline solution. The organic phase is dried over sodium sulfate. The solvent is eliminated and the residue is purified through a silica gel column with a gradient of petroleum ether/ethyl acetate (4:1 to 9:1). Yield: 7.9 g (68% of theory); Rf value: 0.55 (silica gel, petroleum ether/ethyl acetate=3:1); C8H7BrClNO3.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.Cl.[NH2:12][CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([CH3:28])([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:17][CH:16]=1>N1C=CC=CC=1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([CH3:27])([CH3:28])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:17][CH:16]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: CCOC(=O)C(C)(C)c1ccc(CCN)cc1
Agent: Cl
Solvent: c1ccncc1
Product: CCOC(=O)C(C)(C)c1ccc(CCNC(=O)c2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 68 %

Procedure:
9.6 g. 4-Chlorobenzoyl chloride are added dropwise to a solution of 14.1 g ethyl 2-[4-(2-aminoethyl)-phenyl]-2-methylpropionate hydrochloride in 90 ml anhydrous pyridine at 5°-10° C. The reaction mixture is kept at 10° C. for 90 minutes, then allowed to warm up to ambient temperature and subsequently heated to 45° C. for 10 minutes. A part thereof remains undissolved. The reaction mixture is stirred into 750 ml. ice water, filtered with suction and the filter cake then washed. There are obtained 13.2 g (68% of theory) ethyl 2-{4-[2-(4-chlorobenzamido)-ethyl]-phenyl}-2-methylpropionate which, after recrystallization from isopropanol, melts at 108°-109° C.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:10]([CH2:11][S:12]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]([F:25])([F:24])[F:23])(=[O:14])=[O:13])=[CH:9][CH:8]=[CH:7][N:6]=1)=O.O1CCCC1.Cl>C(OC(=O)C)C.C1CCCCC1>[O:14]=[S:12]1(=[O:13])[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]([F:23])([F:25])[F:24])=[C:3]([OH:2])[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:10]2[CH2:11]1
Reactant: COC(=O)c1ncccc1CS(=O)(=O)Cc1ccccc1C(F)(F)F
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: O=S1(=O)Cc2cccnc2C(O)=C1c1ccccc1C(F)(F)F
Reaction time: 3.5 h
Yield: 37.3 %

Procedure:
To a solution of 3-(2-Trifluoromethyl-phenylmethanesulfonylmethyl)-pyridine-2-carboxylic acid methyl ester (7.58 g, 19.6 mmol) in tetrahydrofurane (160 ml) potassium tert-butoxide (2.20 g, 19.57 mmol) was added at room temperature and stirring was continued for 3.5 h. 1M HCl was added, diluted with methylenehloride and extracted. The organic phase was dried with sodiumsulfate and concentrated. Chromatography over silica with ethylacetate/cyclohexane gave 2.50 g colourless crystals (7.32 mmol).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][N:12]=[C:11]([CH3:14])[N:10]=2)[C:5]([OH:8])=[N:6][CH:7]=1.[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[CH2:15]([O:8][C:5]1[C:4]([C:9]2[O:13][N:12]=[C:11]([CH3:14])[N:10]=2)=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Cc1noc(-c2cc(Br)cnc2O)n1
Reactant: BrCc1ccccc1
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: c1ccccc1
Product: Cc1noc(-c2cc(Br)cnc2OCc2ccccc2)n1
Temperature: 20 °C
Reaction time: 6 h

Procedure:
A solution 5-bromo-3-(3-methyl-1,2,4-oxadiazol-5-yl)pyridin-2-ol (1 eq) in benzene (0.05M) was added silver carbonate (1 eq) and benzyl bromide (1.2 eq). The reaction mixture was stirred 6 h at 20° C. and then concentrated. The residue was purified by flash chromatography (Hexane:EtOAc, 90:10) to afforded the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]2[CH:15]=[CH:14][N:13]=[CH:12]2)=[CH:4][CH:3]=1.[O:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH:18]=[C:17]1[C:25]1[O:26][CH:27]=[C:28]([CH2:30]Cl)[N:29]=1>>[O:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH:18]=[C:17]1[C:25]1[O:26][CH:27]=[C:28]([CH2:30][O:1][C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]3[CH:15]=[CH:14][N:13]=[CH:12]3)=[CH:4][CH:3]=2)[N:29]=1
Reactant: ClCc1coc(-c2cc3ccccc3o2)n1
Reactant: Oc1ccc(CCCn2ccnc2)cc1
Product: c1ccc2oc(-c3nc(COc4ccc(CCCn5ccnc5)cc4)co3)cc2c1
Yield: 85 %

Procedure:
In substantially the same manner as in Working Example 72, 1-[3-(4-hydroxyphenyl)propyl]imidazole was allowed to react with 2-(2-benzofuranyl)-4-chloromethyl oxazole to give 2-(2-benzofuranyl)-4-[4-[3-(1-imidazolyl)propyl]phenoxymethyl]oxazole. The yield was 85%. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 122-123° C.
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH3:6])=[O:4].[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[OH:15])#[N:8].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[C:7]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH2:2][C:3]([O:5][CH3:6])=[O:4])#[N:8]
Reactant: COC(=O)CBr
Reactant: N#Cc1ccccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)COc1ccccc1C#N
Temperature: 25 °C
Reaction time: 24 h
Yield: 99.9 %

Procedure:
Methyl bromoacetate (1.95 mL, 20 mmol) is added dropwise to a solution of 2-cyanophenol (2.38 g, 20 mmol), and K2CO3 (2.78 g, 20.1 mmol) in acetone (100 mL) stirred under N2 at 25° C. After 24 h, the solid is filtered off and the filtrate is concentrated in vacuo and the residue is dried in a vacuum oven to give methyl 2-(2-cyanophenoxy)ethanoate (3.82 g, 100%) as a beige solid. 1H NMR (DMSO) δ7.76 (1H, dd, J=7.6, 1.7 Hz), 7.64 (1H, dt, Jd=1.6 Hz, Jt=8.0 Hz), 7.20˜7.10 (2H, m), 5.04 (2H, brs), 3.70 (3H, s).
Reaction SMILES: [CH2:1]([NH:8][C:9](=[O:14])[CH2:10][C:11](=[O:13])[CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[Cl-].[C:18]1([N+:24]#[N:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>O>[CH2:1]([NH:8][C:9](=[O:14])[C:10](=[N:25][NH:24][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:11](=[O:13])[CH3:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#[N+]c1ccccc1
Reactant: CC(=O)CC(=O)NCc1ccccc1
Agent: [Cl-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(=O)C(=NNc1ccccc1)C(=O)NCc1ccccc1
Temperature: 0 °C

Procedure:
7.27 g (0.038) of N-benzyl-3-oxobutyramide were dissolved in a solution of 5.32 g (0.133 mol) of NaOH in 58 ml of water. To the ice-cooled stirred solution, 0.040 mol of phenyldiazonium chloride were added dropwise at such a rate as to keep the temperature at 0° C. The precipitated solid was filtered and recrystallised from MeOH yielding 9 g of the title compound. M.p.=101°-103° C.
Reaction SMILES: FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:19][CH2:18][CH:17]([CH2:20][NH:21][C:22](=[O:39])[CH2:23][S:24][C:25]2[N:30]=[CH:29][C:28]([C:31]3[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=3)=[CH:27][N:26]=2)[CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[NH:15]1[CH2:19][CH2:18][CH:17]([CH2:20][NH:21][C:22](=[O:39])[CH2:23][S:24][C:25]2[N:26]=[CH:27][C:28]([C:31]3[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=3)=[CH:29][N:30]=2)[CH2:16]1
Reactant: COc1ccc(-c2cnc(SCC(=O)NCC3CCN(C(=O)OC(C)(C)C)C3)nc2)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(-c2cnc(SCC(=O)NCC3CCNC3)nc2)cc1
Reaction time: 0.5 h

Procedure:
Neat anhydrous trifluoroacetic acid (3 mL) was added to a solution of N-(1-tert-butoxycarbonylpyrrolidin-3-(RS)-ylmethyl)-2-[5-(4-methoxyphenyl)pyrimidin-2-ylthio]-acetamide (0.60 g, 1.3 mmol) in methylene chloride (20 mL) at room temperature. Gas evolution was apparent immediately upon addition of the acid. After 30 min., the reaction mixture was concentrated using a Teflon dryvac system, and was then further concentrated under high vacuum to give N-(pyrrolidin-3-(RS)-ylmethyl)-2-[5-(4-methoxyphenyl)pyrimidin-2-ylthio]acetamide which was dissolved in 10 mL dichloroethane (0.13 mmol/mL).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][Si](C)(C)C)[C:5]([NH2:8])=[N:6][CH:7]=1.CC([O-])(C)C.[K+].CCOC(C)=O.Cl>CC(O)(C)C.O>[Br:1][C:2]1[CH:3]=[C:4]2[CH:9]=[CH:10][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: C[Si](C)(C)C#Cc1cc(Br)cnc1N
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(C)(C)O
Product: Brc1cnc2[nH]ccc2c1
Temperature: 80 °C
Reaction time: 20 h
Yield: 89.1 %

Procedure:
To a solution of 5-bromo-3-(2-(trimethylsilyl)ethynyl)pyridin-2-amine (B-7-2) (9.5 g, 35.3 mmol) in t-BuOH (100 mL) was added t-BuOK (10.5 g, 141.3 mmol). The mixture was stirred at 80° C. for 20 hours. TLC (Petroleum ether: EtOAc=5:1) showed that the reaction was complete. Then the mixture was cooled to room temperature. Concentrated hydrochoric acid (50 mL) was added to the mixture. Then the mixture was heated to reflux for 8 hours. TLC (Petroleum ether: EtOAc=5:1) showed that the reaction was complete. The mixture was cooled to room temperature and poured into water (100 mL). The mixture was filtered through a bed of Celite. The filtrate was diluted with water (100 mL) and made basic by the addition of 50% sodium hydroxide. The mixture was extracted with EtOAc (150 mL×3). The organic layers were washed with water (100 mL) and saturated sodium chloride (100 mL), dried over sodium sulfate and concentrated under reduced pressure to afford 5-bromo-1H-pyrrolo[2,3-b]pyridine (B-7-3) (6.2 g, 88.6%) as a light yellow solid.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]([CH:11]([OH:24])[C:12](=[NH:23])[NH:13][O:14][C:15](=O)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:9][CH3:10])(C)(C)C.O.C(O)(C(F)(F)F)=O>C(O)C.[OH-].[OH-].[Pd+2]>[NH2:7][CH:8]([CH2:9][CH3:10])[CH:11]([C:12]1[N:23]=[C:15]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:14][N:13]=1)[OH:24]
Reactant: CCC(NC(=O)OC(C)(C)C)C(O)C(=N)NOC(=O)c1ccccc1
Agent: [Pd+2]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Solvent: CCO
Solvent: O
Product: CCC(N)C(O)c1noc(-c2ccccc2)n1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
Compound 3 (9.0 g, 39 mmol) was dissolved in ethanol (100 ml) and water (20 ml) followed by the addition of 9 grams of Pd(OH)2 and TFA (4 ml). The mixture was hydrogenated at 50 psi for 48 hours, then the reaction was filtered through celite which was concentrated to give 9 grams of crude material 4 which was used without further purification. Compound 4 was dissolved in dry methanol (300 ml) and HCl gas was bubbled through for 15 minutes. The reaction was stirred at room temperature for three days and was concentrated. The crude product was purified on silica eluting With 1:1 heptane/ethyl acetate to give 3.9 grains of compound 5.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[CH:5]=[CH:6][C:7]1[C:8]([C:13]([OH:15])=[O:14])=[CH:9][CH:10]=[CH:11][CH:12]=1.[CH3:19]N(C)C=O>[Pd]>[C:13]([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[CH2:6][CH2:5][CH2:4][CH2:3][C:2]1[CH:1]=[CH:19][CH:16]=[CH:17][CH:18]=1)([OH:15])=[O:14]
Reactant: Cc1cccc(C=Cc2ccccc2C(=O)O)c1
Reactant: CN(C)C=O
Agent: [Pd]
Product: O=C(O)c1ccccc1CCCCc1ccccc1

Procedure:
A solution of 53.0 gm. of 3'-methylstilbene-2-carboxylic acid in 230 ml. dimethylformamide containing 2.0 gm. of 5% palladium on carbon is hydrogenated in a Parr shaker at 60 p.s.i. for 11/2 hours. The solution is filtered and added to ether and water. The organic layer is washed with water, then dried and evaporated. The product is recrystallized from ether-hexane to give 48 gm., 90%, of 3-(o-carboxyphenethyl)toluene,m.p. 82°-84° C. Use of 3'-ethylenestilbene-2-carboxylic acid gives a similar yield of 3-(o-carboxyphenethyl)ethylbenzene.
Reaction SMILES: [F:1][CH:2]([F:24])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:15]=[CH:14][C:13](=[O:16])[C:12]([C:17](=O)/[CH:18]=[CH:19]/[N:20](C)C)=[N:11]2)=[CH:6][CH:5]=1.[CH3:25][S:26]([C:29]1[CH:30]=[C:31]([NH:35]N)[CH:32]=[CH:33][CH:34]=1)(=[O:28])=[O:27]>>[F:1][CH:2]([F:24])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:15]=[CH:14][C:13](=[O:16])[C:12]([C:17]3[N:35]([C:31]4[CH:32]=[CH:33][CH:34]=[C:29]([S:26]([CH3:25])(=[O:28])=[O:27])[CH:30]=4)[N:20]=[CH:19][CH:18]=3)=[N:11]2)=[CH:6][CH:5]=1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2ccc(OC(F)F)cc2)ccc1=O
Reactant: CS(=O)(=O)c1cccc(NN)c1
Product: CS(=O)(=O)c1cccc(-n2nccc2-c2nn(-c3ccc(OC(F)F)cc3)ccc2=O)c1

Procedure:
The product was obtained starting from 1-(4-Difluoromethoxy-phenyl)-3-((E)-3-dimethylamino-acryloyl)-1H-pyridazin-4-one (A-9) and (3-methanesulfonyl-phenyl)-hydrazine according to the method described for example 91. MS: M=459.3 (M+H)+
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][CH2:11][CH2:12][N:13]([CH3:33])[CH2:14][CH2:15][C@@:16]1([OH:32])[CH2:25][C:24]([F:27])([F:26])[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([F:28])[CH:22]=2)[C@@H:17]1[CH:29]([CH3:31])[CH3:30].[CH3:34][O:35][CH2:36][C:37](OC1C([2H])([2H])C([2H])([2H])C2C(=CC=C(F)C=2)C1C(C)C)=[O:38]>>[CH3:34][O:35][CH2:36][C:37]([O:32][C@:16]1([CH2:15][CH2:14][N:13]([CH2:12][CH2:11][CH2:10][C:2]2[NH:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[CH3:33])[CH2:25][C:24]([F:27])([F:26])[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([F:28])[CH:22]=2)[C@@H:17]1[CH:29]([CH3:31])[CH3:30])=[O:38]
Reactant: [2H]C1([2H])c2cc(F)ccc2C(C(C)C)C(OC(=O)COC)C1([2H])[2H]
Reactant: CC(C)[C@H]1c2ccc(F)cc2C(F)(F)C[C@]1(O)CCN(C)CCCc1nc2ccccc2[nH]1
Product: COCC(=O)O[C@]1(CCN(C)CCCc2nc3ccccc3[nH]2)CC(F)(F)c2cc(F)ccc2[C@@H]1C(C)C

Procedure:
Compound 104 is prepared from 35d in a manner analogous to that of Example 4 for compound 500.
Reaction SMILES: [C:1]([O-:10])(=[S:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[Na+].Cl[CH2:13][CH2:14][CH2:15][Si:16]([O:23][CH2:24][CH3:25])([O:20][CH2:21][CH3:22])[O:17][CH2:18][CH3:19]>>[C:1]([S:9][CH2:13][CH2:14][CH2:15][Si:16]([O:17][CH2:18][CH3:19])([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22])(=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCC([O-])=S
Reactant: CCO[Si](CCCCl)(OCC)OCC
Agent: [Na+]
Product: CCCCCCCC(=O)SCCC[Si](OCC)(OCC)OCC
Temperature: 90 °C
Reaction time: 5 h

Procedure:
The aqueous solution of sodium thiooctanoate was heated to 40° C. and 11 grams of 34.5% HEGCl solution were added. Also, about 296 grams of 3-chloro-1-propyltriethoxysilane were added batch-wise to the reaction mixture. The product was heated further to 90° C. and stirred for 5 hours. At this point, agitation was discontinued and the two-phase system was allowed to separate. The bottom aqueous phase was removed and the top crude product was recovered. The crude layer was purified by stripping the material at 135-145° C. and 5-10 mm Hg. The process yielded about 251 grams of pale yellow and clear product with a typical GC purity of 92-94%.
Reaction SMILES: [C:1]1([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([I:27])=[CH:23][CH:22]=2)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>[Cu].[N+](C1C=CC=CC=1)([O-])=O>[I:27][C:24]1[CH:25]=[CH:26][C:21]([C:18]2[CH:19]=[CH:20][C:15]([N:7]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[CH:16][CH:17]=2)=[CH:22][CH:23]=1
Reactant: c1ccc(Nc2ccccc2)cc1
Reactant: Ic1ccc(-c2ccc(I)cc2)cc1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=[N+]([O-])c1ccccc1
Product: Ic1ccc(-c2ccc(N(c3ccccc3)c3ccccc3)cc2)cc1
Yield: 55.7 %

Procedure:
16.9 g (0.10 mol) of diphenylamine, 48.7 g (0.12 mol) of 4,4'-diiodobiphenyl, 16.6 g (0.12 mol) of anhydrous potassium carbonate, 1.27 g (0.02 mol) of copper powder, and 20 ml of nitrobenzene were mixed. The reaction mixture was then allowed to undergo reaction at a temperature of 190° C. to 205° C. for 20 hours. The reaction product was then extracted with 200 ml of toluene. The insoluble contents were removed by filtration. The filtrate was then concentrated to dryness. The concentrate was then purified by column chromatography (carrier: silica gel; elute: 1/3 mixture of toluene and n-hexane) to obtain 24.9 g (yield: 55.6%) of N-(4'-iodo-4-biphenylyl)-N,N-diphenylamine. The melting point of the product was from 139.5° C. to 140.5° C.
Reaction SMILES: CCO.[CH3:4][O:5][C:6]([C:8]1[C:9]([OH:32])=[C:10]2[C:15](=[CH:16][N:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13](=[O:25])[C:12]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[CH:11]2)=[O:7]>C1COCC1.[Pd]>[CH3:4][O:5][C:6]([C:8]1[C:9]([OH:32])=[C:10]2[C:15](=[CH:16][N:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13](=[O:25])[CH:12]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:11]2)=[O:7]
Reactant: COC(=O)c1ncc2c(cc(-c3ccccc3)c(=O)n2Cc2ccccc2)c1O
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: COC(=O)c1ncc2c(c1O)CC(c1ccccc1)C(=O)N2Cc1ccccc1
Reaction time: 120 h
Yield: 54.5 %

Procedure:
To a mixture of 10% Pd/C (50 mg) and EtOH (5 mL) was added a solution of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (40 mg, 0.104 mmol) in 5 mL of THF. The resulting mixture was placed under H2 (35 psi) for 5 days. The mixture was filtered through a pad of Celite and the filtrate was concentrated. The residue was purified by silica gel chromatography (0-50% EtOAc/hexanes+2% AcOH) to give 22 mg of the title compound as a white solid. MS: (+) m/z 389.34 (M+1).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[C:4]([OH:9])[C:3]=1[C:10](=[O:12])[CH3:11].C(=O)([O-])[O-].[K+].[K+].[CH2:19](Cl)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C)P(N(C)C)(N(C)C)=O>[CH2:19]([O:8][C:6]1[CH:7]=[C:2]([O:1][CH2:10][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:2]=2)[C:3]([C:10](=[O:12])[CH3:11])=[C:4]([OH:9])[CH:5]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CC(=O)c1c(O)cc(O)cc1O
Reactant: ClCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CC(=O)c1c(O)cc(OCc2ccccc2)cc1OCc1ccccc1
Temperature: 91.5 °C
Yield: 66.5 %

Procedure:
A mixture of 2′,4′,6′-trihydroxyacetophenone (20 g, 0.12 mol, dried in the oven at 140° C.) and anhydrous potassium carbonate (50 g, 0.36 mol) in hexamethylphosphoramide (160 mL) was treated with benzyl chloride (30 mL, 0.26 mol), and the suspension heated at 90-93° C., under an argon atmosphere, for 1.5 h. The mixture was then cooled and filtered. The filtrate was added to 300 mL ice-cold water and acidified to pH 4 with 6N hydrochloric acid. The resulting suspension was heated to 70° C. for 1 h, and then cooled at 4° C. for 16 h. The deposited sticky solid was filtered off and washed with water. This solid was air-dried, and recrystallized from boiling methanol/acetone (2:1). Cooling the solution afforded the product 8 as off-white crystals (27.55 g, 66.5% yield). 1H NMR (300 MHz, CDCl3): δ 2.56 (s, 3H, CH3), 5.06 (s, 4H, CH2), 6.10 and 6.16 (2s, 2H, 3′,5′-Ar—H), 7.40 (m, 10H, Ar—H), 14.01 (s, 1H, OH).