Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:17][C:18]([C:20]2[N:21]=[C:22]([CH3:25])[S:23][CH:24]=2)=[O:19])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7](C1CCCCO1)[CH:6]=2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CC1(C)C(C)(C)OB([C:42]2[CH:50]=[CH:49][CH:48]=[C:47]3[C:43]=2[CH:44]=[N:45][NH:46]3)O1.O1CCOCC1>CO.O>[NH:46]1[C:47]2[CH:48]=[CH:49][CH:50]=[C:42]([C:2]3[CH:10]=[C:9]4[C:5]([CH:6]=[N:7][NH:8]4)=[C:4]([NH:17][C:18]([C:20]4[N:21]=[C:22]([CH3:25])[S:23][CH:24]=4)=[O:19])[CH:3]=3)[C:43]=2[CH:44]=[N:45]1
Reactant: Cc1nc(C(=O)Nc2cc(Br)cc3nn(C4CCCCO4)cc23)cs1
Reactant: CC1(C)OB(c2cccc3[nH]ncc23)OC1(C)C
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: CO
Solvent: O
Product: Cc1nc(C(=O)Nc2cc(-c3cccc4[nH]ncc34)cc3[nH]ncc23)cs1
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
A microwave vial was charged with N-[6-bromo-2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide (50 mg), Solvias catalyst (7 mg), tripotassium phosphate (101 mg), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (available from J&W Pharmlab, 29 mg), 1,4-dioxane (0.5 ml) and water (0.1 ml). The reaction was heated under microwave irradiation for a total of 60 min at 80° C., then 30 min at 120° C. The reaction was passed through a silica cartridge preconditioned with methanol, washing with methanol, then dried in vacuo. The residue was subjected to a DCM/water wash, dried through a hydrophobic frit and dried in vacuo. The residue was dissolved in DMSO:methanol (1 ml, 1:1, v/v) and purified by MDAP (Method D). Appropriate fractions were evaporated under a stream of nitrogen. The residue was dissolved in methanol and a few drops of 2M HCl (aq) were added and the reaction was stirred for 30 min. The reaction was diluted with methanol and passed through an aminopropyl cartridge, pre-conditioned with methanol, washing with methanol, then dried to give title compound, 11 mg.
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[C@H:7]2[O:8][C:9]([CH3:12])([CH3:11])[O:10][C@H:6]2[C@H:5]([N:13]2[CH:21]=[N:20][C:19]3[C:14]2=[N:15][C:16]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[N:17][C:18]=3[NH:22][CH2:23][CH:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[O:4]1.P([O-])(O)(O)=[O:43].[Na+].Cl([O-])=O.[Na+].S([O-])([O-])=O.[Na+].[Na+].Cl>C(#N)C.O.Cl[O-].[Na+]>[C:31]1([CH:24]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:23][NH:22][C:18]2[N:17]=[C:16]([C:37]([O:39][CH2:40][CH3:41])=[O:38])[N:15]=[C:14]3[C:19]=2[N:20]=[CH:21][N:13]3[C@H:5]2[C@@H:6]3[O:10][C:9]([CH3:11])([CH3:12])[O:8][C@@H:7]3[C@@H:3]([C:2]([OH:43])=[O:1])[O:4]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: O=P([O-])(O)O
Reactant: CCOC(=O)c1nc(NCC(c2ccccc2)c2ccccc2)c2ncn([C@@H]3O[C@H](CO)[C@H]4OC(C)(C)O[C@H]43)c2n1
Agent: Cl
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: CCOC(=O)c1nc(NCC(c2ccccc2)c2ccccc2)c2ncn([C@@H]3O[C@H](C(=O)O)[C@H]4OC(C)(C)O[C@H]43)c2n1
Reaction time: 18 h

Procedure:
To a solution of ethyl 9-[(3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-6-[(2,2-diphenylethyl)amino]-9H-purine-2-carboxylate (Preparation 66) (15.4 g, 0.0276 moles) in acetonitrile under an atmosphere of nitrogen was added 2,2,6,6-tetramethylpiperidinyl-1-oxy, free radical (0.30 g, 0.0019 moles) and aqueous sodium dihydrogen phosphate (120 ml of a 0.67M solution). The resultant mixture was heated to 45° C. with stirring. A solution of sodium chlorite (6.5 g, 0.072 moles) in water (75 ml) and a solution of sodium hypochlorite (0.32 ml of commercial solution with 12% w/v available chlorine, 0.000551 moles) in water (38 ml) were added separately and simultaneously to the stirred mixture over a period of 1 hour. The resultant mixture was then stirred at 45–50° C. for 10 hours, and for 18 hours at ambient temperature. The reaction mixture was then added to a solution of sodium sulphite (18 g, 0.143 moles) in water (300 ml) with stirring. After stirring for 5 minutes, the pH was adjusted to 3.7 by the addition of 2M aqueous hydrochloric acid and the mixture was extracted with ethyl acetate (200 ml then 100 ml). The organic phases were combined, dried over anhydrous magnesium sulphate and were then concentrated in vacuo to give the title compound (15.1 g) as a colourless foam that was used as such for the next step. If necessary, this crude product can be purified by standard means, for example by flash chromatography on silica gel.
Reaction SMILES: [H-].[Na+].[CH:3]1([OH:8])[CH2:7][CH2:6][CH2:5][CH2:4]1.[Br:9][CH2:10][CH2:11][CH2:12][CH2:13]Br>C1(C)C=CC=CC=1>[Br:9][CH2:10][CH2:11][CH2:12][CH2:13][O:8][CH:3]1[CH2:7][CH2:6][CH2:5][CH2:4]1
Reactant: BrCCCCBr
Reactant: OC1CCCC1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: BrCCCCOC1CCCC1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
NaH (560 mg, 13.93 mmol, 60% disp. in mineral oil) was washed with hexanes (3×20 mL) in a pressure tube and toluene (6 mL,) was added. The solution was cooled to 0° C. and cyclopentanol (1 g, 11.61 mmol) in toluene (6 mL) was added over 20 min. After stirring at 0° C. for 30 min., 1,4-dibromobutane (1.39 mL, 11.61 mmol) and KI (250 mg) were added. The solution was heated to 100° C. for 14 hours. Upon cooling, the reaction was quenched with NaCl (sat. aq.) and the product extracted with EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated. Purification of the residue via flash column chromatography afforded (4-bromobutoxy)cyclopentane.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([Cl:20])[CH:19]=1.[C:21](=[O:23])=[O:22].[OH-].[Na+]>O1CCCC1.O.CCCCCC>[Cl:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([Cl:20])[C:19]=1[C:21]([OH:23])=[O:22]
Reactant: Clc1cncc(Cl)c1
Reactant: O=C=O
Agent: [Li]CCCC
Agent: [Na+]
Agent: [OH-]
Solvent: CCCCCC
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)c1c(Cl)cncc1Cl
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 70 %

Procedure:
Diisopropylamine (31 mL, 221 mmol) was dissolved in tetrahydrofuran (200 mL), and the solution was added drop-wisely with a 1.6 mol/L hexane solution of n-butyllithium (128 mL, 205 mmol) at −78° C. The mixture was stirred for 15 minutes, and was added drop-wisely with a tetrahydrofuran solution (200 mL) of 3,5-dichloropyridine (25.1 g, 170 mmol) while keeping the temperature at −78° C., and then stirred for additional 1 hour. The reaction solution was added with dry ice to thereby gradually heat to room temperature, and further stirred for 15 hours. The mixture was treated with water (1 L), added with a 1 mol/L aqueous sodium hydroxide solution (100 mL), and washed with ether. The separated aqueous phase was adjusted to be acidic using a 6 mol/L hydrochloric acid, and the resultant precipitate was collected by filtration. The filtrate was extracted with ethyl acetate, the extract was dried over anhydrous sodium sulfate, evaporated under reduced pressure so as to remove the solvent, and the mixture of the resultant residue and the precipitate previously collected were re-crystallized from ethanol, which yielded 3,5-dichloropyridine-4-carboxylic acid (yield: 23 g, yield ratio: 70%) as a yellow crystal.
Reaction SMILES: [C:1]([N:5]1[CH2:10][CH2:9][C:8]2([C:21]3[C:13](=[CH:14][C:15]4[CH2:16][CH2:17][NH:18][C:19]=4[CH:20]=3)[O:12][CH2:11]2)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:22][C:23]1[CH:28]=[C:27]([N:29]2[CH2:33][CH2:32][CH2:31][C:30]2=[O:34])[CH:26]=[CH:25][C:24]=1[C:35]1[CH:40]=[CH:39][C:38]([C:41](O)=[O:42])=[CH:37][CH:36]=1>>[C:1]([N:5]1[CH2:6][CH2:7][C:8]2([C:21]3[C:13](=[CH:14][C:15]4[CH2:16][CH2:17][N:18]([C:41]([C:38]5[CH:37]=[CH:36][C:35]([C:24]6[CH:25]=[CH:26][C:27]([N:29]7[CH2:33][CH2:32][CH2:31][C:30]7=[O:34])=[CH:28][C:23]=6[CH3:22])=[CH:40][CH:39]=5)=[O:42])[C:19]=4[CH:20]=3)[O:12][CH2:11]2)[CH2:9][CH2:10]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)N1CCC2(CC1)COc1cc3c(cc12)NCC3
Reactant: Cc1cc(N2CCCC2=O)ccc1-c1ccc(C(=O)O)cc1
Product: Cc1cc(N2CCCC2=O)ccc1-c1ccc(C(=O)N2CCc3cc4c(cc32)C2(CCN(C(C)(C)C)CC2)CO4)cc1

Procedure:
The title compound was prepared from 1'-tert-butyl-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine) (D61) and 2'-methyl-4'-(2-oxopyrrolidin-1-yl)biphenyl-4-carboxylic acid (D47) using the method outlined in Example 15.
Reaction SMILES: [CH3:1][C@@H:2]([OH:6])[CH2:3][C:4]#[CH:5].[F:7][C:8]1[C:9](I)=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:17])/[C:11]/2=[CH:18]\[C:19]1[NH:23][CH:22]=[N:21][C:20]=1[CH3:24]>CN(C=O)C.CCN(CC)CC.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.[Cu]I>[F:7][C:8]1[C:9]([C:5]#[C:4][CH2:3][C@H:2]([OH:6])[CH3:1])=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=[O:17])/[C:11]/2=[CH:18]\[C:19]1[NH:23][CH:22]=[N:21][C:20]=1[CH3:24]
Reactant: C#CC[C@@H](C)O
Reactant: Cc1nc[nH]c1/C=C1\C(=O)Nc2ccc(F)c(I)c21
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1nc[nH]c1/C=C1\C(=O)Nc2ccc(F)c(C#CC[C@@H](C)O)c21

Procedure:
Using Method C above, (R)-pent-4-yn-2-ol (68 mg, 0.82 mmol) (see Example 78 below) was coupled with (Z)-1,3-dihydro-5-fluoro-4-iodo-3-[(4-methyl-1H-imidazol-5-yl)methylene]-2H-indol-2-one (100 mg, 0.27 mmol) (Starting Material 3 supra) using (Ph3P)4Pd (31 mg, 0.03 mmol) and CuI (6 mg) in a mixture of DMF (5 mL) and Et3N (5 mL) as solvent at 80° C. for 4 hrs. Upon completion, the reaction mixture was concentrated and the residue was chromatographed on a silica gel column with neat CH3CN then THF and finally MeOH as elution solvent. The resulting (R)-(Z)-1,3-Dihydro-5-fluoro-4-(4-hydroxy-1-pentynyl)-3-[(4-methyl-1H-imidazol-5-yl)methylene]-2H-indol-2-one was triturated with Et2O and then recrystalized from superheated EtOH. (Yield 18 mg, 20%).
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[C:8]([CH2:10][C:11]3[N:15]4[N:16]=[C:17]([C:20]5[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=5)[CH:18]=[CH:19][C:14]4=[N:13][CH:12]=3)[CH:7]=[CH:6][C:5]=12.C1C(=O)N([Br:33])C(=O)C1>C(Cl)Cl>[Br:33][C:3]1[N:4]2[CH:9]=[C:8]([CH2:10][C:11]3[N:15]4[N:16]=[C:17]([C:20]5[CH:21]=[N:22][N:23]([CH3:25])[CH:24]=5)[CH:18]=[CH:19][C:14]4=[N:13][CH:12]=3)[CH:7]=[CH:6][C:5]2=[N:1][CH:2]=1
Reactant: Cn1cc(-c2ccc3ncc(Cc4ccc5nccn5c4)n3n2)cn1
Reactant: O=C1CCC(=O)N1Br
Solvent: ClCCl
Product: Cn1cc(-c2ccc3ncc(Cc4ccc5ncc(Br)n5c4)n3n2)cn1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
3-Imidazo[1,2-a]pyridin-6-ylmethyl-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Example 10, 10 mg, 0.030 mmol) was dissolved in DCM (0.3 mL) with NBS (5.9 mg, 0.033 mmol). The RM was stirred at rt for 2 h. The solvent was removed. The residue was purified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and the acetonitrile was removed. The aqueous solution was basified with 5% NaHCO3 solution and it was extracted with EtOAc/MeOH (9:1) twice. Combined organic layers was washed with brine and dried over Na2SO4, filtered and concentrated. The solid obtained was triturated with Et2O. The precipitate was filtered off to afford the title compound as a white solid (tR 0.7 min (conditions 2), MH+=408).
Reaction SMILES: CN(C)CCN[C:6]([C@@H:8]([NH:20][C:21]([C:23]1[CH:42]=[CH:41][C:26]2[N:27]([CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)[C:28]([C:30]3[CH:34]=[CH:33][O:32][CH:31]=3)=[N:29][C:25]=2[CH:24]=1)=[O:22])[CH2:9][C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([OH:19])[CH:17]=2)[NH:12][CH:11]=1)=[O:7].[NH2:44][C:45]([CH3:49])([CH3:48])[CH2:46][OH:47]>>[OH:47][CH2:46][C:45]([NH:44][C:6]([C@@H:8]([NH:20][C:21]([C:23]1[CH:42]=[CH:41][C:26]2[N:27]([CH:35]3[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]3)[C:28]([C:30]3[CH:34]=[CH:33][O:32][CH:31]=3)=[N:29][C:25]=2[CH:24]=1)=[O:22])[CH2:9][C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([OH:19])[CH:17]=2)[NH:12][CH:11]=1)=[O:7])([CH3:49])[CH3:48]
Reactant: CN(C)CCNC(=O)[C@H](Cc1c[nH]c2ccc(O)cc12)NC(=O)c1ccc2c(c1)nc(-c1ccoc1)n2C1CCCCC1
Reactant: CC(C)(N)CO
Product: CC(C)(CO)NC(=O)[C@H](Cc1c[nH]c2ccc(O)cc12)NC(=O)c1ccc2c(c1)nc(-c1ccoc1)n2C1CCCCC1

Procedure:
The carboxylic acid of example 133 was coupled to 2amino-2-methyl-1-propanol under standard TBTU conditions to yield the title compound of example 139.
Reaction SMILES: [C:1]([O:4][CH2:5][CH:6]1[CH:10]([O:11][C:12](=[O:14])[CH3:13])[CH:9]([O:15][C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17])[CH:8]([N:22]2[C:26]3[N:27]=[C:28]([NH:31]C=O)[N:29]=[CH:30][C:25]=3[S:24][C:23]2=[O:34])[O:7]1)(=[O:3])[CH3:2].CC(O)=O>CO>[C:1]([O:4][CH2:5][CH:6]1[CH:10]([O:11][C:12](=[O:14])[CH3:13])[CH:9]([O:15][C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17])[CH:8]([N:22]2[C:26]3[N:27]=[C:28]([NH2:31])[N:29]=[CH:30][C:25]=3[S:24][C:23]2=[O:34])[O:7]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OCC1OC(n2c(=O)sc3cnc(NC=O)nc32)C(OC(=O)OC(C)C)C1OC(C)=O
Solvent: CO
Solvent: CC(=O)O
Product: CC(=O)OCC1OC(n2c(=O)sc3cnc(N)nc32)C(OC(=O)OC(C)C)C1OC(C)=O
Yield: 78.4 %

Procedure:
Acetic acid 3-acetoxy-5-(5-formylamino-2-oxo-thiazolo[4,5-d]pyrimidin-3-yl)-4-isopropoxycarbonyloxy-tetrahydro-furan-2-ylmethyl ester (58) (420 mg, 0.84 mmol) was dissolved in MeOH (8.4 mL), cat. HOAc, and heated to 85° C. for 2 days. The reaction mixture was reduced to an oil in vacuo then subjected to flash chromatography (10-80% EtOAc-hexanes) yielding 310 mg (78%) of 59 as a pure white solid: 1HNMR (400 MHz, DMSO-d6) δ 8.37 (1H, s), 6.88 (2H, bs), 5.91-5.98 (2H, m), 5.47 (1H, dd, J1=5.2 Hz, J2=8.3 Hz), 4.65 (1H, septet, J=6.2 Hz), 4.46-4.51 (1H, m), 4.28 (1H, dd, J1=4.2 Hz, J2=11.9 Hz), 4.18 (1H, dd, J1=7.8 Hz, J2=11.6 Hz), 2.11 (3H, s),2.00 (3H, s), 1.16 (3H, d, J=6.3 Hz), 1.12 (3H, d, J=6.2 Hz).
Reaction SMILES: [OH:1][CH2:2][C:3]([CH3:12])([CH3:11])[C:4]([NH:6][CH2:7][CH2:8][O:9][CH3:10])=[O:5].[N+:13]([C:16]1[CH:23]=[CH:22][CH:21]=[C:20]([N+]([O-])=O)[C:17]=1[C:18]#[N:19])([O-:15])=[O:14]>>[C:18]([C:17]1[C:16]([N+:13]([O-:15])=[O:14])=[CH:23][CH:22]=[CH:21][C:20]=1[O:1][CH2:2][C:3]([CH3:12])([CH3:11])[C:4]([NH:6][CH2:7][CH2:8][O:9][CH3:10])=[O:5])#[N:19]
Reactant: N#Cc1c([N+](=O)[O-])cccc1[N+](=O)[O-]
Reactant: COCCNC(=O)C(C)(C)CO
Product: COCCNC(=O)C(C)(C)COc1cccc([N+](=O)[O-])c1C#N
Yield: 55 %

Procedure:
Prepared as in Example 215c from 3-hydroxy-N-(2-methoxyethyl)-2,2-dimethylpropanamide (Example 225d) and 2,6-dinitrobenzonitrile in 55% yield. MS 322 (MH+).
Reaction SMILES: CO[C:3]([C:5]1[S:6][C:7]([CH:15]=[O:16])=[CH:8][C:9]=1[N:10]=[CH:11][N:12]([CH3:14])C)=[O:4].[CH3:17][N:18]1[CH2:24][CH2:23][CH2:22][N:21]([C:25]2[CH:30]=[CH:29]C(N)=[CH:27][CH:26]=2)[CH2:20][CH2:19]1>>[CH3:17][N:18]1[CH2:24][CH2:23][CH2:22][N:21]([C:25]2[CH:30]=[CH:29][C:14]([N:12]3[C:3](=[O:4])[C:5]4[S:6][C:7]([CH:15]=[O:16])=[CH:8][C:9]=4[N:10]=[CH:11]3)=[CH:27][CH:26]=2)[CH2:20][CH2:19]1
Reactant: COC(=O)c1sc(C=O)cc1N=CN(C)C
Reactant: CN1CCCN(c2ccc(N)cc2)CC1
Product: CN1CCCN(c2ccc(-n3cnc4cc(C=O)sc4c3=O)cc2)CC1

Procedure:
3-(Dimethylaminomethyleneamino)-5-formylthiophene-2-carboxylic acid methyl ester was reacted with 4-(4-methylperhydro-1,4-diazepin-1-yl)phenylamine by method A1. The product with the molecular weight of 368.46 (C19H20N4O2S) was obtained in this way; MS (ESI): 369 (M+H+).
Reaction SMILES: [Br-].[OH:2][CH2:3][CH2:4][CH2:5][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCCCCC.C([Li])CCC.[S:36]1[CH:40]=[CH:39][C:38]([CH:41]=O)=[CH:37]1>O1CCCC1>[S:36]1[CH:40]=[CH:39][C:38](/[CH:41]=[CH:5]/[CH2:4][CH2:3][OH:2])=[CH:37]1
Reactant: OCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccsc1
Agent: [Br-]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: OCC/C=C/c1ccsc1
Reaction time: 0.5 h
Yield: 7.5 %

Procedure:
1.0 g of (3-hydroxypropyl)triphenylphosphonium bromide was dissolved in 20 ml of tetrahydrofuran, and under ice cooling, 3.4 ml of a 15% n-butyllithiumhexane solution was added. After the mixture was stirred for 30 minutes, 270 mg of 3-thiophenecarboxaldhyde was added. The mixture was stirred for 30 minutes, and then the solvent was evaporated. The residue was worked up in a customary manner, and purified by silica gel column chromatography [benzene/ethyl acetate=6/1] to give 28 mg (yield 7%) of the captioned compound as a colorless oil.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[C:11]([CH:13]=O)[CH:10]=[C:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:21]1COCC1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.ClCCl>[CH:13]([C:11]1[CH:10]=[C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:8]=[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:12]=1)=[CH2:21]
Reactant: C1CCOC1
Reactant: O=Cc1cc(-c2ccccc2)cc(-c2ccccc2)c1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: ClCCl
Product: C=Cc1cc(-c2ccccc2)cc(-c2ccccc2)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
3.33 g (0.01289 mol) of [1,1′;3′,1″]terphenyl-5′-carbaldehyde are dissolved in 12 ml of THF and added to methyltriphenylphosphonium bromide solution. The yellowish mixture is stirred at 0° C. for 1 h. After cooling to room temperature, the mixture is taken up in dichloromethane. The solution is washed with water, and the combined organic phases are dried over sodium sulfate. The mixture is evaporated to dryness. Column chromatography is carried out with hexane/ethyl acetate. The column chromatography results in a yield of 2.4 g (71%) of clean substance.
Reaction SMILES: N1C=CC=CC=1.[CH2:7]([O:14][CH2:15][CH:16]([CH3:25])[CH2:17]/[CH:18]=[CH:19]/[CH:20]([CH3:24])[CH2:21][CH2:22][OH:23])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>[O-2].[O-2].[O-2].[Cr+6].ClCCl>[CH2:7]([O:14][CH2:15][CH:16]([CH3:25])[CH2:17]/[CH:18]=[CH:19]/[CH:20]([CH3:24])[CH2:21][CH:22]=[O:23])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CC(/C=C/CC(C)COCc1ccccc1)CCO
Agent: [Cr+6]
Agent: [O-2]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(/C=C/CC(C)COCc1ccccc1)CC=O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 1.19 g. of pyridine in 15 ml. of dichloromethane was added0.6 g. (6 mmoles) of chromium trioxide. The brown mixture was stirred at room temperature for 15 minutes, then treated with a solution of rac. E-8-benzyloxy-3,7-dimethyl-4-octen-1-ol (0.262 g.; 1 mmole) in 3 ml. of dichloromethane. After stirring at room temperature for 15 minutes, the dichloromethane solution was decanted from the dark tarry residue then theresidue was washed three times with fresh dichloromethane. The dichloromethane solutions were combined and washed with 1 N aqueous sodiumhydroxide, 1 N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and brine then dried, filtered and concentrated in vacuo. The residue (0.255 g.) was chromatographed on 10 g. of silica gel. Elution with 9:1 parts by volume and 4:1 parts by volume hexane-ether gave0.196 g. (75.5%) of pure rac. E-8-benzyloxy-3,7-dimethyl-4-octenal. Evaporative distillation yielded a colorless liquid, b.p. 90° -93° C. (bath temperature) (0.1 mm Hg.).
Reaction SMILES: I[C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[CH:9]#[C:10][CH2:11][CH2:12][CH3:13].C(N(CC)CC)C>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu](I)I.C(#N)C>[C:9]([C:2]1[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4])#[C:10][CH2:11][CH2:12][CH3:13]
Reactant: C#CCCC
Reactant: Nc1ccccc1I
Agent: Cl[Pd]Cl
Agent: I[Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCCC#Cc1ccccc1N
Temperature: 25 °C
Reaction time: 2 h
Yield: 68.9 %

Procedure:
A mixture of 2-iodoaniline (500 mg, 2.28 mmol), 1-pentyne (0.27 mL, 2.74 mmol), bis(triphenylphosphine)palladium (II) chloride (77 mg, 0.11 mmol), copper iodide (21 mg, 0.11 mmol), triethylamine (0.95 mL, 6.84 mmol), and acetonitrile (10 mL) was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated under reduced pressure. The residue was stirred in diethyl ether and filtered. The filtrate was concentrated under reduced pressure to afford 0.25 g of 2-pent-1-ynylaniline.
Reaction SMILES: Br[C:2]1[C:3]2[CH2:10][CH2:9][CH:8]([NH:11][S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])[C:4]=2[CH:5]=[N:6][CH:7]=1.[F:17][C:18]([F:29])([F:28])[C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1>>[F:17][C:18]([F:29])([F:28])[C:19]1[CH:24]=[CH:23][C:22]([C:2]2[C:3]3[CH2:10][CH2:9][CH:8]([NH:11][S:12]([CH2:15][CH3:16])(=[O:14])=[O:13])[C:4]=3[CH:5]=[N:6][CH:7]=2)=[CH:21][CH:20]=1
Reactant: CCS(=O)(=O)NC1CCc2c(Br)cncc21
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Product: CCS(=O)(=O)NC1CCc2c(-c3ccc(C(F)(F)F)cc3)cncc21
Yield: 79 %

Procedure:
In analogy to the procedure described for the preparation of example 1, (rac)-N-(4-bromo-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)ethanesulfonamide (intermediate A-7) was reacted with 4-(trifluoromethyl)phenylboronic acid to give the title compound as grey solid in 79% yield. MS: 371.1 (M+H+).
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][C:5]=1[CH:6]=O)([O-:3])=[O:2].[CH2:16]([S:18][C:19]1[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=1[NH2:21])[CH3:17]>C1(C)C=CC=CC=1>[CH2:16]([S:18][C:19]1[CH:25]=[CH:24][CH:23]=[CH:22][C:20]=1[N:21]=[CH:6][C:5]1[CH:8]=[CH:9][C:10]([C:12]([F:15])([F:14])[F:13])=[CH:11][C:4]=1[N+:1]([O-:3])=[O:2])[CH3:17]
Reactant: CCSc1ccccc1N
Reactant: O=Cc1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Solvent: Cc1ccccc1
Product: CCSc1ccccc1N=Cc1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Yield: 96.3 %

Procedure:
A mixture of 500 mg of 2-nitro-4-trifluoromethylbenzaldehyde, 349 mg of 2-(ethylsulfanyl)aniline and 4 ml of toluene was refluxed for 4 hours and then concentrated under reduced pressure. The resulting residue was washed with t-butyl methyl ether to obtain 777 mg of (2-ethylsulfanylphenyl) (2-nitro-4-trifluoromethylbenzylidene)amine.
Reaction SMILES: C(OC([NH:8][C@H:9]([C:19]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]([C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42])[CH2:27][CH2:28][CH2:29][NH:30][C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32])=[O:20])[CH2:10][O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=O)(C)(C)C>FC(F)(F)C(O)=O>[CH2:12]([O:11][CH2:10][C@@H:9]([C:19]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][N:26]([C:41]([O:43][CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)=[O:42])[CH2:27][CH2:28][CH2:29][NH:30][C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32])=[O:20])[NH2:8])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](COCc1ccccc1)C(=O)NCCCCN(CCCNC(=O)OCc1ccccc1)C(=O)OCc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: N[C@@H](COCc1ccccc1)C(=O)NCCCCN(CCCNC(=O)OCc1ccccc1)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
8.00 g (11.5 mmols) of 10-(N-tert-butoxycarbonyl-O-benzyl-L-seryl)-1,5-dibenzyloxycarbonyl-1,5,10-triazadecane was dissolved in 8.0 ml of trifluoroacetic acid, and the solution was stirred for 3 hours at room temperature. The reaction mixture was concentrated under reduced pressure, and the residual oil was dissolved in 200 ml of ethyl acetate. The solution was washed with a 5% aqueous solution of sodium hydrogencarbonate and distilled water in this order, and the ethyl acetate layer was dried over anhydrous sodium sulfate. After the desiccant was removed by filtration, the filtrate was concentrated under reduced pressure to obtain 6.82 g (quantitative) of the desired product as an oily substance.