Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:25])=[C:6]([CH:24]=1)[NH:7][C:8]1[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]=[C:10]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[N:9]=1.[O:26]1[CH2:31][CH2:30][N:29]([C:32]2[CH:40]=[CH:39][C:35]([C:36](O)=[O:37])=[CH:34][CH:33]=2)[CH2:28][CH2:27]1>>[CH3:25][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:36](=[O:37])[C:35]2[CH:34]=[CH:33][C:32]([N:29]3[CH2:30][CH2:31][O:26][CH2:27][CH2:28]3)=[CH:40][CH:39]=2)=[CH:24][C:6]=1[NH:7][C:8]1[CH:13]=[C:12]([C:14]([F:16])([F:17])[F:15])[N:11]=[C:10]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[N:9]=1
Reactant: O=C(O)c1ccc(N2CCOCC2)cc1
Reactant: Cc1ccc(N)cc1Nc1cc(C(F)(F)F)nc(-c2ccncc2)n1
Product: Cc1ccc(NC(=O)c2ccc(N3CCOCC3)cc2)cc1Nc1cc(C(F)(F)F)nc(-c2ccncc2)n1

Procedure:
The title compound was prepared from a mixture of 4-(5-amino-2-methylanilino)-2-(4-pyridinyl)-6-(trifluoromethyl)pyrimidine (10 mg, 0.029 mmol) and 4-morpholinobenzoic acid (7 mg, 0.035 mmol) similar to Example 136 and isolated as a white solid (4 mg, 26%). 1H NMR (CDCl3): 8.76 (dd, J=1.8, 4.2 Hz, 2H), 8.29 (dd, J=1.8, 4.2 Hz, 2H), 7.99 (s, 1H), 7.95 (s, 1H), 7.82 (d, J=9.0 Hz, 2H), 7.37 (dd, J=1.8, 8.1 Hz, 1H), 7.31 (d, J=8.7 Hz, 1H), 7.07 (s, 1H), 6.93 (d, J=9.0 Hz, 2H), 6.73 (s, 1H), 3.89-3.86 (m, 4H), 3.31-3.28 (m, 4H), 2.28 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:27]=[CH:26][C:5]([C:6]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[NH:14][C:13](=[O:18])[CH:12]=[C:11]3[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)=[O:7])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:35][CH:36]1[CH2:38][CH2:37]1>CN(C=O)C.ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[N:14]([CH2:35][CH:36]2[CH2:38][CH2:37]2)[C:13](=[O:18])[CH:12]=[C:11]3[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=2)=[O:7])=[CH:26][CH:27]=1
Reactant: BrCC1CC1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc2[nH]c(=O)cc(-c3cccc(Cl)c3)c2c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(c1ccc(Cl)cc1)c1ccc2c(c1)c(-c1cccc(Cl)c1)cc(=O)n2CC1CC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 67.7 %

Procedure:
A solution of 6-(4-Chloro-benzoyl)-4-(3-chloro-phenyl)-1H-quinolin-2-one (3.10 g, 7.87 mmol), prepared according to the methods described in PCT international patent application publication number WO 97/21701 (published Jun. 19, 1997), in DMF (28 mL) was treated with cesium carbonate (2.56 g, 7.87 mmol) and (bromomethyl)cyclopropane (2.13 g, 15.7 mmol). The reaction mixture was stirred at room temperature for 12 hours, diluted with dichloromethane (25 mL), and washed with 1N HCl (2×10 mL) and brine (20 mL). The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo to give a black residue. Purification by flash column chromatography (silica, ethyl acetate:petroleum ether 1:9-3:7) gave 6-(4-Chloro-benzoyl)-4-(3-chloro-phenyl)-1-cyclopropylmethyl-1H-quinolin-2-one (2.39 g, 68%) as an off-white foam.
Reaction SMILES: [Cl:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6](Cl)=[O:7])=[C:4]([F:12])[CH:3]=1.Cl.[F:14][C:15]([F:20])([F:19])[C@H:16]([NH2:18])[CH3:17].C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([NH:18][C@H:16]([CH3:17])[C:15]([F:20])([F:19])[F:14])=[O:7])=[C:4]([F:12])[CH:3]=1
Reactant: O=C(Cl)c1cc(F)c(Cl)cc1F
Reactant: C[C@@H](N)C(F)(F)F
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: C[C@@H](NC(=O)c1cc(F)c(Cl)cc1F)C(F)(F)F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
4-Chloro-2,5-difluorobenzoyl chloride (29.6 mg, 0.140 mmol) (Oakwood, Cat. #: 001628) was added to a solution of (2R)-1,1,1-trifluoropropan-2-amine hydrochloride (20.0 mg, 0.134 mmol) (SynQuest Lab, Cat. #: 3130-7-R1) in methylene chloride (4.0 mL) at 0° C. The reaction mixture was stirred at room temperature for 30 min., then worked up with saturated aqueous NaHCO3, and extracted with dichloromethylene. The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure to afford the desired product which was directly used in the next step reaction without further purification. LCMS (M+H)+: m/z=288.0/289.9.
Reaction SMILES: [C:1]1([C:13]2[C:14](=[O:33])[NH:15][C:16](=[O:32])[C:17]=2[C:18]2[C:26]3[O:25][CH:24]=[CH:23][C:22]=3[C:21]([O:27][CH2:28][CH2:29][CH2:30]O)=[CH:20][CH:19]=2)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1.C(Br)(Br)(Br)[Br:35].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[C:1]1([C:13]2[C:14](=[O:33])[NH:15][C:16](=[O:32])[C:17]=2[C:18]2[C:26]3[O:25][CH:24]=[CH:23][C:22]=3[C:21]([O:27][CH2:28][CH2:29][CH2:30][Br:35])=[CH:20][CH:19]=2)[C:11]2=[C:12]3[C:7](=[CH:8][CH:9]=[CH:10]2)[CH2:6][CH2:5][CH2:4][N:3]3[CH:2]=1
Reactant: O=C1NC(=O)C(c2ccc(OCCCO)c3ccoc23)=C1c1cn2c3c(cccc13)CCC2
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: O=C1NC(=O)C(c2ccc(OCCCBr)c3ccoc23)=C1c1cn2c3c(cccc13)CCC2
Reaction time: 0.17 h
Yield: 98.9 %

Procedure:
Dissolve 3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]-quinolin-1-yl)-4-(4-(3-(hydroxy)propoxy)benzofur-7-yl)-2,5-dioxopyrrole (0.1 g, 0.232 mmol) in 10 mL dichloromethane. Add carbon tetrabromide (0.077 g) and triphenylphosphine (0.061 g). Stir for 10 minutes and add another equivalent of both reagents. Stir 10 minutes then dilute with dichloromethane and wash with water followed by saturated aqueous sodium chloride. Dry over magnesium sulfate then filter and concentrate under reduced pressure. Subject residue to silica gel chromatography, eluting with 2% methanol in dichloromethane to provide the desired compound (0.116 g)
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10](I)[C:9]([OH:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[C:14]([Si:18]([CH3:21])([CH3:20])Cl)(C)(C)C>>[Cl:1][C:2]1[CH:11]=[C:10]([Si:18]([CH3:21])([CH3:20])[CH3:14])[C:9]([OH:13])=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: Oc1c(I)cc(Cl)c2cccnc12
Product: C[Si](C)(C)c1cc(Cl)c2cccnc2c1O

Procedure:
The title compound is prepared in two steps from 5-chloro-8-hydroxy-7-iodoquinoline, which is commercially available, according to the procedures described in Preparation 11 and Example 41, substituting trimethylchlorosilane for t-butyldimethylchlorosilane in the former procedure. Column chromatography (elution with 0-1% EtOAc/hexane) gives 0.147 g of the title compound as a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[CH:12]=[CH:13][C:14](=[O:16])[CH3:15].[BH4-].[Na+].O>C(O)C>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[CH:6]=[CH:5][C:4]=1[CH:12]=[CH:13][CH:14]([OH:16])[CH3:15]
Reactant: COc1cc([N+](=O)[O-])ccc1C=CC(C)=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: COc1cc([N+](=O)[O-])ccc1C=CC(C)O
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.8 %

Procedure:
To a suspension of 4-(2-methoxy-4-nitrophenyl)but-3-en-2-one (12.2 g; 55.2 mmol) in 150 mL of ethanol at rt was added NaBH4 (2.30 g; 60.7 mmol) over 5 minutes. The suspension was stirred at rt for 1 h, diluted with 1M NaHPO4 (˜60 mL) followed by water (100 mL) and concentrated under reduced pressure to remove ethanol. After extracting the aqueous residue with CH2Cl2, the organic layer was washed with water and brine, dried over anhydrous MgSO4, filtered. Concentration of the filtrate under reduced pressure afforded 12.3 g (100%) of the title compound as a dark, red gum. HPLC (Method #1) 3.68 min retention time, (50%); MS (ES): m/z 206 [M−OH]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH:9]=[N:10][O:11][CH2:12][CH2:13][CH3:14])[CH:3]=1.[C:15]([O-])(=[O:17])[CH3:16].[Na+]>C(OC(=O)C)(=O)C>[C:15]([O:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=1[CH:9]=[N:10][O:11][CH2:12][CH2:13][CH3:14])(=[O:17])[CH3:16]
Reactant: CCCON=Cc1cc(Cl)ccc1O
Reactant: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)OC(C)=O
Product: CCCON=Cc1cc(Cl)ccc1OC(C)=O
Temperature: 25 °C
Yield: 70.4 %

Procedure:
To a stirred solution of 6.4 grams (0.03 mole) of 4-chloro-2-[(propoxyimino)methyl]phenol (prepared in the manner of Example 1) in 50 ml of acetic anhydride was added in one portion 2.5 grams (0.03 mole) of sodium acetate. The reaction mixture was heated at 90°-100° for two hours, cooled to ambient temperature, and poured into 200 ml of ice-water. The mixture was stirred until the ice melted. A colorless oil separated and was extracted with portions of methylene chloride. The combined extracts were dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil. The oil was distilled under reduced pressure to give 5.4 grams of 4-chloro-2-[(propoxyimino)methy]phenyl acetate; bp 95°-107°/3.333 Pa.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH3:18])=[CH:13][CH:12]=1.[Cl:19][CH2:20][C:21](Cl)=[O:22]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]([C:21](=[O:22])[CH2:20][Cl:19])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH3:18])=[CH:13][CH:12]=1
Reactant: O=C(Cl)CCl
Reactant: CCc1ccc(Nc2c(C)cc(Cl)cc2Cl)cc1
Solvent: Cc1ccccc1
Product: CCc1ccc(N(C(=O)CCl)c2c(C)cc(Cl)cc2Cl)cc1
Temperature: 100 °C

Procedure:
N-(2′,4′Dichloro-6′-methylphenyl)-4-ethylaniline (4.83 g as a mixture with the byproduct N,N-di-(4-ethylphenyl)-2′,4′-dichloro-6′-methylaniline) is dissolved in 4.18 g of chloro acetylchlorid and heated to 100° C. for 1.5 h. The mixture is cooled, diluted with toluene (50 ml) and extracted with aqu. sodium bicarbonate. The organic phase is evaporated to dryness and chromatographed on silica (75 g) eluting with toluene to afford unreacted N,N-di-(4-ethylphenyl)-2′,4′-dichloro-6′-methylaniline and N-(2′,4-dichloro-6′-methylphenyl)-N-chloroacetyl-4-ethylaniline (2.95 g). A crystallised sample melts at 83-84° C.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([CH3:16])([CH3:15])[CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].C(Br)(Br)(Br)[Br:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:18][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([CH3:16])([CH3:15])[CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: CCOC(=O)CCC(C)(C)CCCCCO
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCOC(=O)CCC(C)(C)CCCCCBr
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of ethyl 9-hydroxy-4,4-dimethylnonanoate (example 285, step f) (0.44 g) in DCM (19 mL) at 0° C. was treated with carbon tetrabromide (0.76 g) followed by triphenylphosphine (0.60 g) and the reaction mixture was stirred at room temperature overnight. Further amounts of carbon tetrabromide (0.76 g) and triphenylphosphine (0.60 g) were added and stirring continued for 3 hours. The solvent was removed by evaporation then the mixture was triturated with cyclohexane and the resultant solid removed by filtration. The solid was washed with cyclohexane and the filtrate was concentrated to about 15 mL and left to stand overnight. The solid which came out of solution was removed by filtration, washed with cyclohexane and the filtrate evaporated to afford the subtitled compound as a pale brown oil. Yield 0.56 g.
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5](P(OC)(OC)=O)[NH:6][C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])=[O:4].CN(C)C(=N)N(C)C.[C:31]([O:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([CH:47]=O)=[CH:44][CH:45]=2)[CH:40]=[N:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]>O1CCCC1>[C:31]([O:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([CH:47]=[C:5]([NH:6][C:7]([O:9][CH2:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=3)=[O:8])[C:3]([O:2][CH3:1])=[O:4])=[CH:44][CH:45]=2)[CH:40]=[N:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32]
Reactant: CC(C)(C)OC(=O)n1ncc2cc(C=O)ccc21
Reactant: COC(=O)C(NC(=O)OCc1ccccc1)P(=O)(OC)OC
Agent: CN(C)C(=N)N(C)C
Solvent: C1CCOC1
Product: COC(=O)C(=Cc1ccc2c(cnn2C(=O)OC(C)(C)C)c1)NC(=O)OCc1ccccc1
Temperature: -78 °C
Reaction time: 4 h
Yield: 84.6 %

Procedure:
A solution of N-(benzyloxycarbonyl)-α-phosphonoglycine trimethyl ester (5.50 g, 16.6 mmol) and tetramethylguanidine (1.99 mL, 15.9 mmol) in anhydrous tetrahydrofuran (50 mL) was stirred at −78° C. for 20 min. To this was added a solution of 5-formyl-indazole-1-carboxylic acid tert-butyl ester (3.72 g, 15.1 mmol) in tetrahydrofuran (25 mL) slowly via syringe over 10 min. The reaction mixture was stirred at −78° C. for 4 h and then allowed to warm to room temperature overnight. The solvent was evaporated and the resulting residue subjected to flash column chromatography on silica gel (1:2 ethyl acetate/hexane) giving the title compound as a white foam (5.77 g, 85%). 1H-NMR (CDCl3, 500 MHz) δ 8.09 (d, J=9.0 Hz, 1H), 8.08 (s, 1H), 7.84 (s, 1H), 7.67 (d, J=9.0 Hz, 1H), 7.47 (s, 1H), 7.30 (br s, 5H), 6.43 (br s, 1H), 5.09 (s, 2H), 3.84 (s, 3H), 1.72 (s, 9H). Mass spec.: 452 (MH)+.
Reaction SMILES: Br[C:2]1[N:7]=[C:6]2[N:8]([CH2:11][C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[N:18]=[CH:17][CH:16]=[CH:15]4)[N:9]=[N:10][C:5]2=[N:4][CH:3]=1.[NH:22]1[CH2:26][CH2:25][CH:24]([OH:27])[CH2:23]1.C(N(CC)CC)C>CC(O)C>[N:18]1[C:19]2[C:14](=[CH:13][C:12]([CH2:11][N:8]3[C:6]4=[N:7][C:2]([N:22]5[CH2:26][CH2:25][CH:24]([OH:27])[CH2:23]5)=[CH:3][N:4]=[C:5]4[N:10]=[N:9]3)=[CH:21][CH:20]=2)[CH:15]=[CH:16][CH:17]=1
Reactant: Brc1cnc2nnn(Cc3ccc4ncccc4c3)c2n1
Reactant: OC1CCNC1
Solvent: CCN(CC)CC
Solvent: CC(C)O
Product: OC1CCN(c2cnc3nnn(Cc4ccc5ncccc5c4)c3n2)C1
Temperature: 70 °C
Yield: 99.5 %

Procedure:
A mixture of 6-((6-bromo-1H-[1,2,3]triazolo[4,5-b]pyrazin-1-yl)methyl)quinoline (5.00 g, 14.7 mmol), pyrrolidin-3-ol (2.55 g, 29.3 mmol), and triethylamine (4.09 mL, 29.3 mmol) in 2-propanol (32 mL) was heated in the microwave for 30 minutes at 70° C. in two vials. The reaction mixtures were combined and concentrated. The crude product was purified by flash chromatography using a Horizon purification system in three batches (2×40M and 1×40S columns) eluting with chloroform/methanol (0.1-8%). The resulting solid was dissolved in chloroform containing 0.1% methanol (810 mL) and washed with water and 1:1 water:brine, dried (MgSO4), filtered and concentrated to afford 1-[1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]pyrrolidin-3-ol (5.08 g, 99%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:37]=[C:36]([O:38][CH3:39])[CH:35]=[CH:34][C:4]=1[CH2:5][N:6]([C:29]1[S:33][N:32]=[CH:31][N:30]=1)[S:7]([C:10]1[CH:18]=[C:17]2[C:13]([C:14](B3OC(C)(C)C(C)(C)O3)=[CH:15][N:16]2[CH3:19])=[CH:12][CH:11]=1)(=[O:9])=[O:8].P([O-])([O-])([O-])=O.[K+].[K+].[K+].[Cl:48][C:49]1[CH:54]=[C:53]([C:55]([F:58])([F:57])[F:56])[CH:52]=[CH:51][C:50]=1I>C(OCC)(=O)C.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[Cl:48][C:49]1[CH:54]=[C:53]([C:55]([F:56])([F:57])[F:58])[CH:52]=[CH:51][C:50]=1[C:14]1[C:13]2[C:17](=[CH:18][C:10]([S:7]([N:6]([CH2:5][C:4]3[CH:34]=[CH:35][C:36]([O:38][CH3:39])=[CH:37][C:3]=3[O:2][CH3:1])[C:29]3[S:33][N:32]=[CH:31][N:30]=3)(=[O:8])=[O:9])=[CH:11][CH:12]=2)[N:16]([CH3:19])[CH:15]=1
Reactant: FC(F)(F)c1ccc(I)c(Cl)c1
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2ccc3c(B4OC(C)(C)C(C)(C)O4)cn(C)c3c2)c(OC)c1
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: COc1ccc(CN(c2ncns2)S(=O)(=O)c2ccc3c(-c4ccc(C(F)(F)F)cc4Cl)cn(C)c3c2)c(OC)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 74.2 %

Procedure:
A vial was charged with N-(2,4-dimethoxybenzyl)-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (0.500 g, 0.876 mmol), potassium phosphate (0.651 g, 3.07 mmol), and bis(tri-t-butylphosphine)palladium(0) (0.045 g, 0.088 mmol). The vial was flushed with Ar, then 1,4-dioxane (6.57 ml) and water (2.191 ml) were added in sequence, followed by 2-chloro-1-iodo-4-(trifluoromethyl)benzene (0.426 ml, 2.63 mmol). The vial was sealed and stirred at room temperature for two hours. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried with sodium sulfate, filtered and concentrated. The material was purified via column chromatography (RediSep Gold (Teledyne Isco, Lincoln, Nebr.) 40 g, gradient elution 0-100% EtOAc/Heptane) to afford 3-(2-chloro-4-(trifluoromethyl)phenyl)-N-(2,4-dimethoxybenzyl)-1-methyl-N-(1,2,4-thiadiazol-5-yl)-1H-indole-6-sulfonamide (0.405 g, 0.650 mmol, 74.2% yield) as a light yellow solid. m/z (ESI) 624.0 (M+H)+.
Reaction SMILES: [C:1]1([C:7]([C:10]2[CH:11]=[N:12][C:13]3[C:18]([C:19]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:17][CH:16]=[CH:15][C:14]=3[C:26]([F:29])([F:28])[F:27])(O)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.O>CCO>[C:20]1([C:19]2[C:18]3[C:13](=[C:14]([C:26]([F:29])([F:27])[F:28])[CH:15]=[CH:16][CH:17]=3)[N:12]=[CH:11][C:10]=2[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH2:8])[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CC(O)(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1ccccc1
Agent: Cl
Solvent: CCO
Solvent: O
Product: C=C(c1ccccc1)c1cnc2c(C(F)(F)F)cccc2c1-c1ccccc1
Yield: 84.6 %

Procedure:
1-phenyl-1-[4-phenyl-8-(trifluoromethyl)quinolin-3-yl]ethanol (0.675 g, 1.72 mmol) in EtOH (13 mL) is refluxed with conc HCl (2.6 mL) for 2 h. The cooled reaction is poured into water and extracted with methylene chloride. The extract is washed with saturated aq sodium bicarbonate, dried (MgSO4) and concentrated. The residue is chromatographed eluting with 5:95 ethyl acetate:hexane to afford the title compound as a yellow solid (0.546 g, 85%). MS (ESI) m/z 376; HRMS: calcd for C24H16F3N+H, 376.13131; found (ESI, [M+H]+), 376.1306.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:32]2[N:36]([C:37]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[N:35]=[N:34][N:33]=2)[N:5]([C:7]2[CH:12]=[CH:11][C:10]([CH2:13][O:14][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:9][CH:8]=2)[CH:6]=1.C([Li])CCC.Cl[C:62]([O:64][CH2:65][CH3:66])=[O:63]>O1CCCC1.CN(C)CCN(C)C>[Si:15]([O:14][CH2:13][C:10]1[CH:11]=[CH:12][C:7]([N:5]2[CH:6]=[C:2]([C:62]([O:64][CH2:65][CH3:66])=[O:63])[CH:3]=[C:4]2[C:32]2[N:36]([C:37]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[N:35]=[N:34][N:33]=2)=[CH:8][CH:9]=1)([C:28]([CH3:29])([CH3:31])[CH3:30])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: CC(C)(C)[Si](OCc1ccc(-n2cc(Br)cc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1)(c1ccccc1)c1ccccc1
Reactant: CCOC(=O)Cl
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCOC(=O)c1cc(-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)n(-c2ccc(CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)cc2)c1
Reaction time: 2 h

Procedure:
To a stirred solution of 4-bromo-1-(4-tert-butyldiphenylsilyloxymethylphenyl)-2-(1-trityl-1H-tetrazol-5-yl)pyrrole (500 mg) in a mixture of tetrahydrofuran (5 ml) and N,N,N',N'-tetramethylethylenediamine (0.19 ml) was added n-butyl lithium (0.41 ml; 1.6M in n-hexane) at -78° C. under nitrogen atmosphere and the mixture was stirred at the same temperature for half an hour. Ethyl chloroformate (0.3 ml) was added to the mixture at the same temperature and the resulting mixture was stirred at -78° C. for half an hour, at 0° C. for one hour and then at ambient temperature for two hours. The reaction was quenched with aqueous saturated sodium bicarbonate and diluted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. After filtration, the filtrate was concentrated and the residue was purified by flash chromatography eluted with a mixture of ethyl acetate-n-hexane 1:9 (V/V) to give 1-(4-tert-butyldiphenylsilyloxymethylphenyl)-4-ethoxycarbonyl-2-(1-trityl-1H-tetrazol-5-yl)pyrrole (311 mg) as a colorless viscous oil.
Reaction SMILES: [CH2:1]([OH:14])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(Cl)Cl>[CH:1](=[O:14])/[CH:2]=[CH:3]/[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCCCCCCC/C=C/CO
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CCCCCCCCCC/C=C/C=O

Procedure:
To undecyl aldehyde (5.0 g) dissolved in methylene chloride was added (carbomethoxymethylene )triphenylphosphorane (14.7 g), and the mixture was stirred for 2 hours. The reaction mixture was concentrated and subjected to chromatography on a silica gel column with eluent systems of n-hexane-ethyl acetate (from 100:1 to 20:1) to give the methyl ester of trans-2-tridecenoic acid (55.2 g). To the methyl ester dissolved in tetrahydrofuran was added lithium aluminum hydride (0.9 g) under ice-cooling, and the mixture was stirred for 1 hour. The reaction mixture was distributed into ethyl acetate and water, and the ethyl acetate layer was dried, concentrated and subjected to chromatography on a silica gel column with an eluent system of n-hexane-ethyl acetate (50:1) to give trans-2-tridecenol (3.2 g). To the solution of the trans-2-tridecenol in methylene chloride were added pyridinium chlorochromate (3.2 g) and Celite (5.0 g), and the mixture was stirred. The reaction mixture was filtered and concentrated to give trans-2-tridecenal (1.7 g).
Reaction SMILES: [I:1]N1C(=O)CCC1=O.[NH2:9][C:10]1[C:15]2[C:16]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[C:21]([O:33][CH3:34])[CH:20]=3)=[CH:17][O:18][C:14]=2[CH:13]=[CH:12][N:11]=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>CN(C)C=O>[NH2:9][C:10]1[C:15]2[C:16]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[C:21]([O:33][CH3:34])[CH:20]=3)=[CH:17][O:18][C:14]=2[C:13]([I:1])=[CH:12][N:11]=1
Reactant: COc1cc(-c2coc3ccnc(N)c23)ccc1NC(=O)OC(C)(C)C
Reactant: O=C1CCC(=O)N1I
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc(-c2coc3c(I)cnc(N)c23)ccc1NC(=O)OC(C)(C)C
Reaction time: 18 h
Yield: 83.9 %

Procedure:
N-Iodosuccinimide (0.333 g, 1.48 mmol) was added to a solution of tert-butyl 4-(4-aminofuro[3,2-c]pyridin-3-yl)-2-methoxyphenylcarbamate (0.439 g, 1.24 mmol) in N,N-dimethylformamide (10 mL) at ambient temperature. The reaction suspension was stirred for 18 hours, at which time no starting material remained. An aqueous solution of 10% sodium thiosulfate (10 mL) was added to the suspension and stirred for 30 minutes. The precipitate was collected by vacuum filtration and washed with water. The solid was dried in vacuo to give the title compound (0.501 g, 84%) as a tan solid. 1H NMR (DMSO-d6, 400 MHz) δ 8.08 (s, 1H), 8.07 (s, 1H), 8.06 (s, 1H), 7.85 (d, 1H), 7.13 (d, 1H), 7.04, (dd, 1H), 5.73–5.80 (bs, 2H), 3.86 (s, 3H), 1.48 (s, 9H); RP-HPLC (Conditions d) Rt 8.49 min.; MS: MH+ 482.