Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:13]2[CH:26]=[CH:25][C:16]([O:17][CH2:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[C:15]([CH3:27])[CH:14]=2)([CH2:11][CH3:12])[CH2:9][CH3:10])=[CH:4][C:3]=1[CH3:28].[Cl:29][CH2:30][CH2:31][S:32](Cl)(=[O:34])=[O:33].C(N(CC)CC)C>>[CH3:21][C:20]([CH3:22])([CH3:23])[C:19](=[O:24])[CH2:18][O:17][C:16]1[CH:25]=[CH:26][C:13]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([NH:1][S:32]([CH2:31][CH2:30][Cl:29])(=[O:34])=[O:33])=[C:3]([CH3:28])[CH:4]=2)([CH2:11][CH3:12])[CH2:9][CH3:10])=[CH:14][C:15]=1[CH3:27]
Reactant: O=S(=O)(Cl)CCCl
Reactant: CCC(CC)(c1ccc(N)c(C)c1)c1ccc(OCC(=O)C(C)(C)C)c(C)c1
Solvent: CCN(CC)CC
Product: CCC(CC)(c1ccc(NS(=O)(=O)CCCl)c(C)c1)c1ccc(OCC(=O)C(C)(C)C)c(C)c1
Yield: 98.4 %

Procedure:
Using a procedure analogous to Example 17, 1-{4-[1-(4-amino-3-methyl-phenyl)-1-ethyl-propyl]-2-methyl-phenoxy}-3,3-dimethyl-butan-2-one (382 mg, 1 mmol), 2-chloro-ethanesulfonyl chloride (0.1 mL, 1 mmol) and triethylamine (0.14 mL, 1 mmol) give the title compound as a oil (500 mg, quant.)
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:14]=[CH:13][C:12]([CH:15]([CH2:18][CH3:19])[C:16]#[N:17])=[CH:11][CH:10]=2)[O:3]1.B.C1COCC1>>[CH3:7][C:6]1([CH3:8])[C:2]([CH3:1])([CH3:20])[O:3][B:4]([C:9]2[CH:14]=[CH:13][C:12]([CH:15]([CH2:18][CH3:19])[CH2:16][NH2:17])=[CH:11][CH:10]=2)[O:5]1
Reactant: CCC(C#N)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Agent: B
Solvent: C1CCOC1
Product: CCC(CN)c1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Yield: 93 %

Procedure:
Following the procedure outlined for Example 666, 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)butanenitrile (3.4 g, 12.5 mmol) was reacted with BH3.THF (1.0 M in THF, 64 mL, 64 mmol) to afford the desired product (3.2 g, 93%) as light yellow oil: ESI MS m/z 276 [C16H26BNO2+H]+.
Reaction SMILES: [CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[C:15]3[CH:21]([CH3:22])[CH2:20][CH2:19][CH2:18][C:16]=3[S:17][C:11]=2[N:10]=[C:9]1[C:23]1[CH:28]=[C:27]([O:29][CH3:30])[C:26]([O:31][CH3:32])=[C:25]([O:33][CH3:34])[CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=C[NH+]=CC=1.[O-:41][Cr](Cl)(=O)=O>ClCCl>[CH2:1]([N:8]1[C:13](=[O:14])[C:12]2[C:15]3[CH:21]([CH3:22])[CH2:20][CH2:19][C:18](=[O:41])[C:16]=3[S:17][C:11]=2[N:10]=[C:9]1[C:23]1[CH:24]=[C:25]([O:33][CH3:34])[C:26]([O:31][CH3:32])=[C:27]([O:29][CH3:30])[CH:28]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[Cr](=O)([O-])Cl
Reactant: COc1cc(-c2nc3sc4c(c3c(=O)n2Cc2ccccc2)C(C)CCC4)cc(OC)c1OC
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: COc1cc(-c2nc3sc4c(c3c(=O)n2Cc2ccccc2)C(C)CCC4=O)cc(OC)c1OC

Procedure:
3-Benzyl-5-methyl-2-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one (Compound No. 683) (17.7 mmol) dissolved in dry dichloromethane (30 ml) was added quickly to a mixture of PCC (19.2 g, 89.0 mmol, 500 mol-%) in dichloromethane (200 ml). During refluxing PCC was added several times until the reaction was completed. The reaction mixture was filtered through Celite with dichloromethane. The crude product was purified by flash chromatography.
Reaction SMILES: C(O)(=O)C.Cl.C([CH2:9][C:10]1(C)[C:23](=[O:24])[C:22]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][C:13]=2[CH2:12][CH2:11]1)(O)=O>O>[CH3:9][CH:10]1[C:23](=[O:24])[C:22]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=[CH:14][C:13]=2[CH2:12][CH2:11]1
Reactant: CC1(CC(=O)O)CCc2ccc3ccccc3c2C1=O
Agent: Cl
Solvent: O
Solvent: CC(=O)O
Product: CC1CCc2ccc3ccccc3c2C1=O
Yield: 95 %

Procedure:
In a 1-neck 500 ml flask topped with a reflux condenser 250 ml of acetic acid, 50 ml of conc. hydrochloric acid and 50 ml of water were mixed together. To this mixture was added 27.7 g (0.0846 mole) of 3-carboxymethyl-3methyl-1,2,3,4-tetrahydro-4-phenanthron and the reaction mixture was refluxed for 31/2 hours under nitrogen. The mixture was diluted with 300 ml water and cooled in the refrigerator overnight. Next morning offwhite solids were collected by filtration, washed with water and dried under vacuum to give 16.9 g (95.02% by weight yield) of 3-methyl-1,2,3,4-tetrahydro-4-phenanthrone as an off-white solid. M.P. 61°-63° C.; M/e 211; λmax 309 (6,970) methanol.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[CH:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+]>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:2]1([C:2]2[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]=2)[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[CH:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1
Reactant: FC(F)(F)Oc1ccc(-n2cnc(-c3ccc(Br)cc3)n2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: FC(F)(F)Oc1ccc(-n2cnc(-c3ccc(C4=CCCCC4)cc3)n2)cc1

Procedure:
The title compound was prepared as described in Example 10 using 3-(4-bromophenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C52) with tetrakis(triphenylphosphine)palladium(0) as catalyst, sodium carbonate as base and heating to 100° C. for 3 hours; isolated as an orange solid (2.18 g, 57%, 79% pure): 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.15-8.06 (m, 2H), 7.80 (dd, J=9.0, 2.3 Hz, 2H), 7.50 (d, J=8.4 Hz, 2H), 7.39 (ddd, J=8.0, 2.5, 1.3 Hz, 2H), 6.28-6.21 (m, 1H), 2.46 (ddt, J=6.3, 4.1, 2.0 Hz, 2H), 2.24 (dtd, J=6.3, 3.8, 1.8 Hz, 2H), 1.85-1.75 (m, 2H), 1.71-1.63 (m, 2H); 19F NMR (376 MHz, DMSO-d6) δ −58.03; ESIMS m/z 386 ([M+H]+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]=[C:10]2[C:19]3[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=3[NH:13][C:12](=O)[N:11]2[CH:21]=1.O=P(Cl)(Cl)[Cl:24]>>[Cl:24][C:12]1[N:11]2[CH:21]=[C:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[N:9]=[C:10]2[C:19]2[CH2:18][CH2:17][CH2:16][CH2:15][C:14]=2[N:13]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1[nH]c2c(c3nc(-c4ccccc4F)cn13)CCCC2
Product: Fc1ccccc1-c1cn2c(Cl)nc3c(c2n1)CCCC3

Procedure:
To 50 mL of POCl3 was added 2-(2-Fluorophenyl)-7,8,9,10-tetrahydro-imidazo[1,2-c]-quinazolin-5(6H)-one (600 mg) and the resultant mixture was refluxed for 48 h. The mixture was then cooled and the POCl3 was removed in vacuo. To the residue was added 20 mL of water and the pH adjusted to 7 with ammonium hydroxide. After cooling, the precipitated solid was collected to yield 5-Chloro-2-(2-fluorophenyl)-7,8,9,10-tetrahydro-imidazo[1,2-c]-quinazoline (Compound 30), m.p. 175°-176° C.
Reaction SMILES: [C:1]([C:6]1[CH:11]=[CH:10][C:9]([S:12]([N:15]2[CH2:19][CH2:18][S:17][CH:16]2[C:20]([OH:22])=O)(=[O:14])=[O:13])=[CH:8][CH:7]=1)([CH2:4][CH3:5])([CH3:3])[CH3:2].[NH2:23][C@H:24]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:25][CH2:26][OH:27]>>[OH:27][CH2:26][CH2:25][C@H:24]([NH:23][C:20]([C@H:16]1[N:15]([S:12]([C:9]2[CH:8]=[CH:7][C:6]([C:1]([CH2:4][CH3:5])([CH3:3])[CH3:2])=[CH:11][CH:10]=2)(=[O:13])=[O:14])[CH2:19][CH2:18][S:17]1)=[O:22])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CCC(C)(C)c1ccc(S(=O)(=O)N2CCSC2C(=O)O)cc1
Reactant: N[C@@H](CCO)c1ccccc1
Product: CCC(C)(C)c1ccc(S(=O)(=O)N2CCS[C@H]2C(=O)N[C@@H](CCO)c2ccccc2)cc1

Procedure:
Following the general strategies and protocols outlined in Example 1, starting from 3-[(4-tert-pentylphenyl)sulfonyl]-1,3-thiazolidine-2-carboxylic acid (Intermediate 8) and commercial (3S)-3-amino-3-phenyl-1-propanol, the title compound was obtained in 99% purity by HPLC.
Reaction SMILES: [C:1]1([CH2:7][CH:8]([NH:14][C:15](=[O:33])[C:16]2[CH:21]=[CH:20][CH:19]=[N:18][C:17]=2[N:22]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[N:23]2)[CH:9]([OH:13])[C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:36]=[C:35]1[CH2:43][NH2:44]>>[O:34]1[C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=2[N:36]=[C:35]1[CH2:43][NH:44][C:10](=[O:12])[CH:9]([OH:13])[CH:8]([NH:14][C:15](=[O:33])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][C:17]=1[N:22]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[N:23]1)[CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NCc1nc2ccccc2o1
Reactant: O=C(NC(Cc1ccccc1)C(O)C(=O)O)c1cccnc1-n1ccc(-c2ccccc2)n1
Product: O=C(NC(Cc1ccccc1)C(O)C(=O)NCc1nc2ccccc2o1)c1cccnc1-n1ccc(-c2ccccc2)n1

Procedure:
The reaction was carried out in analogy to reaction step 1.3 by reacting 4-phenyl-2-hydroxy-3-(2-(3-phenyl-1H-pyrazol-1-yl)nicotinamido)butanoic acid with benzo[d]oxazol-2-ylmethylamine; ESI-MS [M+H]+: 573.2
Reaction SMILES: Br[C:2]1[C:10]2[C:9]([NH:11][C@H:12]([C:14]3[N:19]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:18](=[O:26])[C:17]4=[C:27]([CH3:30])[CH:28]=[CH:29][N:16]4[N:15]=3)[CH3:13])=[N:8][CH:7]=[N:6][C:5]=2[N:4]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:3]=1.[F:39][C:40]1[CH:41]=[C:42]([NH:55][S:56]([CH3:59])(=[O:58])=[O:57])[CH:43]=[C:44](B2OC(C)(C)C(C)(C)O2)[CH:45]=1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:39][C:40]1[CH:41]=[C:42]([NH:55][S:56]([CH3:59])(=[O:57])=[O:58])[CH:43]=[C:44]([C:2]2[C:10]3[C:9]([NH:11][C@H:12]([C:14]4[N:19]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[C:18](=[O:26])[C:17]5=[C:27]([CH3:30])[CH:28]=[CH:29][N:16]5[N:15]=4)[CH3:13])=[N:8][CH:7]=[N:6][C:5]=3[N:4]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[CH:3]=2)[CH:45]=1
Reactant: CC1(C)OB(c2cc(F)cc(NS(C)(=O)=O)c2)OC1(C)C
Reactant: Cc1ccn2nc([C@H](C)Nc3ncnc4c3c(Br)cn4COCC[Si](C)(C)C)n(-c3ccccc3)c(=O)c12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: Cc1ccn2nc([C@H](C)Nc3ncnc4c3c(-c3cc(F)cc(NS(C)(=O)=O)c3)cn4COCC[Si](C)(C)C)n(-c3ccccc3)c(=O)c12
Yield: 64 %

Procedure:
(S)-2-(1-((5-Bromo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)ethyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (50 mg, 0.08 mmol) was treated with N-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanesulfonamide (67 mg, 0.21 mmol, described at WO 2004052847 A2 20040624), sodium carbonate (23 mg, 0.22 mmols) and bis(triphenylphosphine)palladium(II) dichloride (21 mg, 0.03 mmol) according to the method described in Preparation 62. The residue was purified using SP1® Purification System (0% to 100%, hexane-ethyl ether) to give 36 mg (61% yield) of the title compound. Purity 100%.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([C:11]2[N:12]=[C:13]([CH2:16]O)[S:14][CH:15]=2)[CH:8]=[C:7]([C:18]([CH3:21])([CH3:20])[CH3:19])[C:6]=1[OH:22])([CH3:4])([CH3:3])[CH3:2].C(Br)(Br)(Br)[Br:24].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>ClCCl>[Br:24][CH2:16][C:13]1[S:14][CH:15]=[C:11]([C:9]2[CH:10]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:6]([OH:22])=[C:7]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:8]=2)[N:12]=1
Reactant: CC(C)(C)c1cc(-c2csc(CO)n2)cc(C(C)(C)C)c1O
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)c1cc(-c2csc(CBr)n2)cc(C(C)(C)C)c1O
Temperature: 0 °C
Yield: 92 %

Procedure:
1.5 g (4.70 mmol) of intermediate 334.2, (2,6-ditert-butyl-4-[2-(hydroxymethyl)-1,3-thiazol-4-yl]phenol is dissolved in dichloromethane (30 ml). After adding CBr4 (2.02 g; 6.10 mmol), the reaction medium is cooled down to 0° C. PPh3 (1.48 g; 5.63 mmol) is added by fractions then the mixture is left to return to ambient temperature. The reaction medium is then poured into ice-cooled water before being extracted with dichloromethane. The organic phase is washed with salt water before being dried over magnesium sulphate, filtered and concentrated under vacuum. The expected product is obtained after chromatography on a silica column (eluent: 30% of ethyl acetate in heptane), in order to produce a brown oil with a yield of 92%. This product is sufficiently pure to be used directly in the following stage.
Reaction SMILES: C([O-])(=O)C.[NH4+:5].[CH2:6]([C:9]1[N:10]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29]CC)=O)[C:11]2[C:20]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N:14]=[CH:13][C:12]=2[N:21]=1)[CH2:7][CH3:8].C(=O)(O)[O-].[Na+]>>[CH2:6]([C:9]1[N:10]([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([NH2:5])=[O:29])[C:11]2[C:20]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N:14]=[CH:13][C:12]=2[N:21]=1)[CH2:7][CH3:8]
Reactant: [NH4+]
Reactant: CCCc1nc2cnc3ccccc3c2n1CCCCCC(=O)OCC
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Product: CCCc1nc2cnc3ccccc3c2n1CCCCCC(N)=O
Temperature: 25 °C
Yield: 45.2 %

Procedure:
Ammonium acetate (20 g) and ethyl 6-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)hexanoate (4.11 g, 11.6 mmol) were heated overnight at 140° C. in a sealed vessel. The reaction was allowed to cool to ambient temperature, and saturated aqueous sodium bicarbonate was added. The mixture was extracted with chloroform (3×), and the extracts were combined and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 95:5 dichloromethane:methanol) to provide 1.7 g of 6-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)hexanamide.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:11](I)=[CH:10][N:9]([CH2:13][C:14]3[C:19]([CH3:20])=[C:18]([O:21][CH3:22])[C:17]([CH3:23])=[CH:16][N:15]=3)[C:4]=2[N:5]=[C:6]([NH2:8])[N:7]=1.[CH2:24]([OH:30])[CH2:25][CH2:26][CH2:27][C:28]#[CH:29]>>[NH2:8][C:6]1[N:7]=[C:2]([Cl:1])[C:3]2[C:11]([C:29]#[C:28][CH2:27][CH2:26][CH2:25][CH2:24][OH:30])=[CH:10][N:9]([CH2:13][C:14]3[C:19]([CH3:20])=[C:18]([O:21][CH3:22])[C:17]([CH3:23])=[CH:16][N:15]=3)[C:4]=2[N:5]=1
Reactant: COc1c(C)cnc(Cn2cc(I)c3c(Cl)nc(N)nc32)c1C
Reactant: C#CCCCCO
Product: COc1c(C)cnc(Cn2cc(C#CCCCCO)c3c(Cl)nc(N)nc32)c1C

Procedure:
The title compound was prepared by Sonogashira coupling of 4-chloro-5-iodo-7-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamine (see Example 1) with 5-hexyn-1-ol according to the General Procedure A. tR: 4.92 min. 1H-NMR (DMSO-d6) δ 8.04 (s, 1H), 7.22 (s, 1H), 6.69 (br. s, 2H), 5.25 (s, 2H), 4.39 (t, 1H), 3.70 (s, 3H), 3.40 (q, 2H), 2.39 (t, 2H), 2.23 (s, 3H), 2.14 (s, 3H), 1.55 (m, 4H).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH:9]2[CH2:13][CH2:12][CH2:11][CH2:10]2)=[N:6][CH:7]=1.[B:14](OC(C)C)([O:19]C(C)C)[O:15]C(C)C.[Li]CCCC.Cl>O.C1(C)C=CC=CC=1.C1COCC1>[CH:9]1([O:8][C:5]2[N:6]=[CH:7][C:2]([B:14]([OH:19])[OH:15])=[CH:3][CH:4]=2)[CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: Brc1ccc(OC2CCCC2)nc1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Solvent: Cc1ccccc1
Product: OB(O)c1ccc(OC2CCCC2)nc1
Temperature: -70 °C
Reaction time: 0.67 h
Yield: 46.4 %

Procedure:
To a mixture of 5-bromo-2-cyclopentoxypyridine (2.5 g, 10.3 mmol, see step (b) above), B(O-iPr)3 (2.33 g, 13.4 mmol), THF (4.1 mL) and toluene (16.5 mL) was portion-wise-added BuLi (2.5 M in hexane; 4.96 ml, 13.4 mmol) at −70° C. over 1 h. The reaction mixture was stirred over a further 40 min at −70° C. and then allowed to warm to −20° C. The acidity of the reaction mixture was adjusted to about pH 1 by addition of HCl (2 M aq. solution). The reaction was diluted with water (50 mL) and extracted with Et2O (2×50 mL). The pH of the water phase was then adjusted to about pH 7 by the addition of NaOH (5 M aq. solution). Brine was added and the product was extracted with EtOAc (4×50 mL). Removal of the solvent afforded the sub-title compound (0.99 g, 46%).
Reaction SMILES: [CH3:1][CH:2]([NH:20][C:21](=[O:23])[CH3:22])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]#[C:11][C:12]2[CH:17]=[CH:16][N:15]=[C:14]([S:18][CH3:19])[N:13]=2)=[CH:6][CH:5]=1.ClC1C=C(C=CC=1)C(OO)=[O:29].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:19][S:18]([C:14]1[N:13]=[C:12]([C:11]#[C:10][C:7]2[CH:6]=[CH:5][C:4]([CH2:3][CH:2]([NH:20][C:21](=[O:23])[CH3:22])[CH3:1])=[CH:9][CH:8]=2)[CH:17]=[CH:16][N:15]=1)=[O:29]
Reactant: CSc1nccc(C#Cc2ccc(CC(C)NC(C)=O)cc2)n1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(=O)NC(C)Cc1ccc(C#Cc2ccnc(S(C)=O)n2)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A mixture of 0.30 g (0.922 mmol) N-{1-methyl-2-[4-(2-methylsulfanyl-pyrimidin-4-ylethynyl)-phenyl]-ethyl}-acetamide (example 14.1) in 9 mL DCM is cooled down to 0° C. and charged with 0.27 g (1.10 mmol; 70% purity) 3-chloroperoxybenzoic acid. The mixture is stirred for 30 min at constant temperature. The mixture is poured onto sat. aq. NaHCO3 solution. The organic layer is separated, dried with Na2SO4 and filtered. The resulting mixture can be used directly used in the following reaction.
Reaction SMILES: [NH:1]1[C:5]2=[C:6]([NH:10][C:11](=[O:13])[CH3:12])[N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[Cl:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:16]=1[C:17](Cl)=[O:18]>>[Cl:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:16]=1[C:17]([C:3]1[C:4]2[C:5](=[C:6]([NH:10][C:11](=[O:13])[CH3:12])[N:7]=[CH:8][CH:9]=2)[NH:1][CH:2]=1)=[O:18]
Reactant: CC(=O)Nc1nccc2cc[nH]c12
Reactant: O=C(Cl)c1c(F)cccc1Cl
Product: CC(=O)Nc1nccc2c(C(=O)c3c(F)cccc3Cl)c[nH]c12

Procedure:
N-[3-(2-Chloro-6-fluorobenzoyl)-1H-pyrrolo[2,3-c]pyridin-7-yl]acetamide was prepared analogously using N-(1H-pyrrolo[2,3-c]pyridin-7-yl)acetamide and 2-chloro-6-fluoro benzoyl chloride (Compound No. 8).
Reaction SMILES: [C:1](=[O:13])([O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH3:12])[O:2][CH2:3]I.[Na].[F:15][C:16]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:17]=1[CH2:23][NH:24][C:25]([C:27]1[C:28](=[O:43])[C:29]([OH:42])=[C:30]2[C:35](=[O:36])[N:34]3[C@@H:37]([CH3:40])[CH2:38][O:39][C@@H:33]3[CH2:32][N:31]2[CH:41]=1)=[O:26].C(=O)([O-])[O-].[K+].[K+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[C:1](=[O:13])([O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][CH3:12])[O:2][CH2:3][O:42][C:29]1[C:28](=[O:43])[C:27]([C:25]([NH:24][CH2:23][C:17]2[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:16]=2[F:15])=[O:26])=[CH:41][N:31]2[C:30]=1[C:35](=[O:36])[N:34]1[C@@H:37]([CH3:40])[CH2:38][O:39][C@@H:33]1[CH2:32]2
Reactant: C[C@H]1CO[C@@H]2Cn3cc(C(=O)NCc4ccc(F)cc4F)c(=O)c(O)c3C(=O)N12
Reactant: COCCOCCOC(=O)OCI
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: O=S(=O)([O-])O
Product: COCCOCCOC(=O)OCOc1c2n(cc(C(=O)NCc3ccc(F)cc3F)c1=O)C[C@H]1OC[C@H](C)N1C2=O

Procedure:
The title compound was prepared from iodomethyl 2-{[2-(methyloxy)ethyl]oxy}ethyl carbonate (57 mg, 0.187 mmol), 1b (40 mg, 0.094 mmol), potassium carbonate (39 mg, 0.281 mmol), and tetrabutylammonium hydrogen sulfate (32 mg, 0.094 mmol), using a similar process to that described in example 1. 1H NMR (CDCl3) δ 10.21 (m, 1H), 8.44 (s, 1H), 7.32 (m, 1H), 6.81 (m, 2H), 5.93 (d, J=6.4 Hz, 1H), 5.83 (d, J=6.4 Hz, 1H), 5.30 (dd, J=10, 3.6 Hz, 1H), 4.59 (m, 2H), 4.43-4.27 (m, 5H), 3.93 (m, 1H), 3.77-3.61 (m, 5H), 3.52 (m, 2H), 3.35 (s, 3H), 1.38 (d, J=6.4 Hz, 3H). ES+ MS: 582 (M+1).
Reaction SMILES: C[O:2][C:3](=[O:37])[C:4]1[CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:7]=[C:6]([O:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH:5]=1.[OH-].[Na+]>CO.O1CCOCC1>[CH2:19]([O:18][C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([O:10][CH2:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:7]=1)[C:3]([OH:37])=[O:2])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]
Reactant: CCCCCCCCCCCCCCCCCCOc1cc(OCc2ccccc2)cc(C(=O)OC)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1COCCO1
Product: CCCCCCCCCCCCCCCCCCOc1cc(OCc2ccccc2)cc(C(=O)O)c1
Yield: 98.2 %

Procedure:
A mixture of 46.3 g (0.091 mol) of 3-(octadecyloxy)-5-(phenylmethoxy)benzoic acid methyl ester and 45 ml (0.27 mol) of 6N NaOH in 750 ml of methanol and 300 ml of dioxane was stirred at reflux for 4 hours. The reaction mixture was filtered and the filtrate was concentrated at reduced pressure. The residue was suspended in water, acidified and filtered to give 44.4 g (99% yield, mp 97°-99°) of 3-(octadecyloxy)-5-(phenylmethoxy)benzoic acid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][N:13]([C@@H:18]([CH:23]([CH3:25])[CH3:24])[C:19]([O:21][CH3:22])=[O:20])[C:14]3=[O:17])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[F:26][C:27]1[CH:28]=[C:29]([S:34](Cl)(=[O:36])=[O:35])[CH:30]=[CH:31][C:32]=1[F:33]>>[F:26][C:27]1[CH:28]=[C:29]([S:34]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[CH:16]=[C:15]4[C:11]([CH2:12][N:13]([C@@H:18]([CH:23]([CH3:25])[CH3:24])[C:19]([O:21][CH3:22])=[O:20])[C:14]4=[O:17])=[CH:10][CH:9]=3)=[CH:6][CH:7]=2)(=[O:35])=[O:36])[CH:30]=[CH:31][C:32]=1[F:33]
Reactant: O=S(=O)(Cl)c1ccc(F)c(F)c1
Reactant: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(N)cc3)cc2C1=O
Product: COC(=O)[C@H](C(C)C)N1Cc2ccc(-c3ccc(NS(=O)(=O)c4ccc(F)c(F)c4)cc3)cc2C1=O

Procedure:
The compound of example 81 was prepared analogous to compound of example 77 by reaction of compound of example 6 with 3,4-difluorobenzene sulfonyl chloride. The compound of example 81 was used directly without isolation for the preparation of compound of example 82.
Reaction SMILES: [CH:1]1[C:14]2[C@H:13]3[CH:15]([OH:18])[CH:16]([OH:17])[C@H:6]([C:7]4[C:12]3=[CH:11][CH:10]=[CH:9][CH:8]=4)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.C([O-])(=O)C.[Pb+4]>C(O)(=O)C>[CH:1]1[C:14]2[C:5](=[C:6]([CH:16]=[O:17])[C:7]3[C:12]([C:13]=2[CH:15]=[O:18])=[CH:11][CH:10]=[CH:9][CH:8]=3)[CH:4]=[CH:3][CH:2]=1
Reactant: OC1C(O)[C@H]2c3ccccc3[C@@H]1c1ccccc12
Agent: CC(=O)[O-]
Agent: [Pb+4]
Solvent: CC(=O)O
Product: O=Cc1c2ccccc2c(C=O)c2ccccc12
Reaction time: 2 h

Procedure:
A solution of 2.38 g. (0.01 mole) of cis-9,10-dihydro-9,10-ethanoanthracene-11,12-diol [Newman et al., J. Am. Chem. Soc., 77, 3789 (1955)] in 50 ml. of glacial acetic acid was stirred magnetically at 30°-35° C. and treated portionwise with 8.9 g. (0.02 mole) of lead tetra-acetate or until a blue color persisted with starch-iodide test paper. The reaction mixture was stirred for two hours and the so-formed orange crystals were removed by filtration and recrystallized from methylene chloride giving 1.5 g. (65%) of orange needles, m.p. 245°-247° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([N:24]3[CH:28]=[CH:27][CH:26]=[N:25]3)=[CH:20][CH:19]=2)[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[S:30]1[CH:34]=[CH:33][N:32]=[C:31]1[S:35](Cl)(=[O:37])=[O:36]>>[C:1]([O:5][C:6](=[O:29])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][N:16]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([N:24]3[CH:28]=[CH:27][CH:26]=[N:25]3)=[CH:22][CH:23]=2)[S:35]([C:31]2[S:30][CH:34]=[CH:33][N:32]=2)(=[O:37])=[O:36])[CH:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)COc1cccc(CNCc2ccc(-n3cccn3)cc2)c1
Reactant: O=S(=O)(Cl)c1nccs1
Product: CC(C)(C)OC(=O)COc1cccc(CN(Cc2ccc(-n3cccn3)cc2)S(=O)(=O)c2nccs2)c1

Procedure:
The title compound of Step A was prepared following the method described in Step B of Example 3 from {3-[(4-pyrazol-1-yl-benzylamino)-methyl]-phenoxy}-acetic acid tert-butyl ester, prepared in Step A of Example 13a, and thiazole-2-sulfonyl chloride, of Preparation 45 with a reaction time of 3 h. 1H NMR (400 MHz, CD3OD) δ 7.95 (d, 1H), 7.87 (d, 1H), 7.69 (m, 1H), 7.59 (dd, 1H), 7.54 (d, 2H), 7.15 (m, 3H), 6.74 (m, 3H), 6.44 (m, 1H), 4.49 (s, 2H), 4.46 (s, 2H), 4.42 (s, 2H), 1.49 (s, 9H); MS 541 (M+1).