Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][OH:25])[CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[C:26]([O:29][CH2:30][C:31]1[C:32]([N:46]2[CH2:58][CH2:57][N:49]3[C:50]4[CH2:51][CH2:52][CH2:53][CH2:54][C:55]=4[CH:56]=[C:48]3[C:47]2=[O:59])=[N:33][CH:34]=[CH:35][C:36]=1B1OC(C)(C)C(C)(C)O1)(=[O:28])[CH3:27].[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC([O-])=O.[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CC#N.O>[C:26]([O:29][CH2:30][C:31]1[C:32]([N:46]2[CH2:58][CH2:57][N:49]3[C:50]4[CH2:51][CH2:52][CH2:53][CH2:54][C:55]=4[CH:56]=[C:48]3[C:47]2=[O:59])=[N:33][CH:34]=[CH:35][C:36]=1[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][OH:25])[CH2:19][CH2:18]3)=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1)(=[O:28])[CH3:27]
Reactant: CC(=O)OCc1c(B2OC(C)(C)C(C)(C)O2)ccnc1N1CCn2c(cc3c2CCCC3)C1=O
Reactant: Cn1cc(Br)cc(Nc2ccc(N3CCN(CCO)CC3)cn2)c1=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(=O)[O-]
Solvent: O
Solvent: CC#N
Product: CC(=O)OCc1c(-c2cc(Nc3ccc(N4CCN(CCO)CC4)cn3)c(=O)n(C)c2)ccnc1N1CCn2c(cc3c2CCCC3)C1=O

Procedure:
A sealed tube was charged with 123c (200 mg, 0.49 mmol), 3-(acetoxymethyl)-2-(1-oxo-3,4,6,7,8,9-hexahydropyrazino[1,2-a]indol-2(1H)-yl)pyridin-4-ylboronic acid (113i) (188 mg, 0.49 mmol), Pd(dppf)Cl2 (40 mg, 0.049 mmol), K3PO4 (208 mg, 0.98 mmol), NaOAc (133 mg, 0.98 mmol), H2O (3 mL), and MeCN (50 mL). The mixture was heated at 110° for 3 h. The solvent was evaporated in vacuo and the residue was purified by silica gel chromatography eluting with 30:1 DCM/MeOH to 123d (187 mg, 57%). MS: [M+H]+ 667.7.
Reaction SMILES: [F:1]C(F)(N(CC)CC)C(F)C(F)(F)F.[CH3:15][N:16]([CH3:32])[C:17]([C@@H:19]1[CH2:23][C@H:22](O)[CH2:21][N:20]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[O:18].[F-].[Na+].C(=O)([O-])O.[Na+]>ClCCl.C(OCC)(=O)C.CCCCCC>[CH3:15][N:16]([CH3:32])[C:17]([C@@H:19]1[CH2:23][C@@H:22]([F:1])[CH2:21][N:20]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[O:18]
Reactant: CCN(CC)C(F)(F)C(F)C(F)(F)F
Reactant: CN(C)C(=O)[C@@H]1C[C@H](O)CN1C(=O)OC(C)(C)C
Agent: O=C([O-])O
Agent: [F-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: ClCCl
Product: CN(C)C(=O)[C@@H]1C[C@@H](F)CN1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 15 h

Procedure:
8.85 g of a mixture (approximately 3:1) of 1,1,2,3,3,3-hexafluoro-1-(diethylamino)propane and 1,2,3,3,3-pentafluoro-1-(diethylamino)-2-propene was added dropwise over a period of 2 minutes under ice cooling to a suspension of 8.54 g of the compound obtained in step 1-1b and 1.67 g of sodium fluoride in 90 mL of dichloromethane, after which the reaction mixture was stirred for 15 hours at room temperature. 200 mL of a saturated sodium hydrogencarbonate aqueous solution was added dropwise to the reaction solution over a period of 3 minutes, and the reaction mixture was stirred for 1 hour. After liquid separation, the aqueous layer was extracted with chloroform (30 mL×2), and the combined organic layer was washed with 50 mL of saturated brine and dried with magnesium sulfate, after which the drying agent was filtered off and the reaction mixture was concentrated under reduced pressure. The residue thus obtained was subjected to column chromatography (silica gel 60, mobile phase: ethyl acetate/n-hexane=1/1 to 10/0; v/v) to obtain 7.54 g of the titled compound (pale yellow solid).
Reaction SMILES: O.[NH2:2][NH2:3].[CH2:4]([NH:11][C:12](SC)=[C:13]([C:16]#[N:17])[C:14]#[N:15])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.CS>CO>[NH2:15][C:14]1[NH:3][N:2]=[C:12]([NH:11][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:13]=1[C:16]#[N:17]
Reactant: CSC(NCc1ccccc1)=C(C#N)C#N
Reactant: NN
Agent: CS
Solvent: CO
Solvent: O
Product: N#Cc1c(NCc2ccccc2)n[nH]c1N
Temperature: 25 °C
Reaction time: 2 h

Procedure:
24 ml (0.48 mol) of hydrazine hydrate are added dropwise to a solution of 92 g (0.4 mol) of 3-benzylamino-3-methylsulfanyl-2-cyano-acrylonitrile in 400 ml of methanol, the temperature rising to 40° C. The reaction mixture is slowly heated to boiling (e evolution of MeSH!), boiled for 2 hours, cooled to RT and concentrated by evaporation to a residual volume of ≈200 ml. Dilution with diethyl ether, filtration and washing with diethyl ether yield 5-amino-3-benzylamino-1H-pyrazole-4-carbonitrile [Spectrochimica Acta, 47A, 1635 (1991)]; m.p. 150-152° C.; TLC: Rf=0.41 (ethyl acetate).
Reaction SMILES: N[C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:5]=2[N:6]=1.[Br-:13].[K+].N([O-])=O.[Na+]>S(=O)(=O)(O)O>[Br:13][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[C:5]=2[N:6]=1
Reactant: [Br-]
Reactant: COc1cccc2sc(N)nc12
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: COc1cccc2sc(Br)nc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 78.8 %

Procedure:
To a solution of 2-amino-4-methoxybenzothiazole (1.5 g) and potassium bromide (3.5 g) in sulphuric acid (1.25M, 50 ml) at 0° C. was added sodium nitrite (0.86 g) over a period of 1 hr. The reaction was allowed to warm to room temperature and stirred for 2 hrs, before being extracted with dichloromethane (3×50 ml). The combined organic extracts were dried over magnesium sulphate (5 g), and the solvent removed in vacuo to yield an off white solid. This was purified by flash chromatography (eluent 50% ethyl acetate/hexane) to yield the title compound as a white solid (1.6 g). TLC Ff 0.30 (20% ethyl acetate in hexane)
Reaction SMILES: [F:1][C:2]([F:34])([F:33])[C:3]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][C:4]=1[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([CH:15]=[C:16]3[S:20][C:19](SCC)=[N:18][C:17]3=[O:24])=[CH:12][CH:13]=2)[CH:8]=[N:7]1.[C:35]([O:39][C:40]([N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH:43]1[C:48](=[O:52])[NH:49][O:50][CH3:51])=[O:41])([CH3:38])([CH3:37])[CH3:36]>>[C:35]([O:39][C:40]([N:42]1[CH2:47][CH2:46][N:45]([C:19]2[S:20][C:16](=[CH:15][C:11]3[CH:10]=[C:9]4[C:14](=[CH:13][CH:12]=3)[N:6]([CH2:5][C:4]3[CH:25]=[CH:26][C:27]([C:29]([F:30])([F:31])[F:32])=[CH:28][C:3]=3[C:2]([F:1])([F:33])[F:34])[N:7]=[CH:8]4)[C:17](=[O:24])[N:18]=2)[CH2:44][CH:43]1[C:48](=[O:52])[NH:49][O:50][CH3:51])=[O:41])([CH3:38])([CH3:37])[CH3:36]
Reactant: CCSC1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(C(F)(F)F)cc3C(F)(F)F)c2)S1
Reactant: CONC(=O)C1CNCCN1C(=O)OC(C)(C)C
Product: CONC(=O)C1CN(C2=NC(=O)C(=Cc3ccc4c(cnn4Cc4ccc(C(F)(F)F)cc4C(F)(F)F)c3)S2)CCN1C(=O)OC(C)(C)C

Procedure:
4-{5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-yl}-2-methoxycarbamoyl-piperazine-1-carboxylic acid tert-butyl ester was prepared from 5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-ethylsulfanyl-thiazol-4-one and 2-Methoxycarbamoyl-piperazine-1-carboxylic acid tert-butyl ester following General Procedure C.
Reaction SMILES: COC1C=CC(C[N:8](CC2C=CC(OC)=CC=2)[C:9]2[CH:10]=[C:11]([C:16]([CH:21]([C:26]([O:28][CH3:29])=[O:27])[C:22]([O:24][CH3:25])=[O:23])([CH:18]3[CH2:20][CH2:19]3)[CH3:17])[CH:12]=[CH:13][C:14]=2[Cl:15])=CC=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.C(=O)(O)[O-].[Na+]>ClCCl.O>[NH2:8][C:9]1[CH:10]=[C:11]([C:16]([CH:21]([C:26]([O:28][CH3:29])=[O:27])[C:22]([O:24][CH3:25])=[O:23])([CH:18]2[CH2:19][CH2:20]2)[CH3:17])[CH:12]=[CH:13][C:14]=1[Cl:15]
Reactant: COC(=O)C(C(=O)OC)C(C)(c1ccc(Cl)c(N(Cc2ccc(OC)cc2)Cc2ccc(OC)cc2)c1)C1CC1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: COC(=O)C(C(=O)OC)C(C)(c1ccc(Cl)c(N)c1)C1CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
627 mg (1.11 mmol) of dimethyl (1-{3-[bis(4-methoxybenzyl)amino]-4-chlorophenyl}-1-cyclo-propylethyl)malonate were taken up in 60 ml of dichloromethane and 15 ml of water. 553 mg (2.44 mmol) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) were then added, and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was then added to about 50 ml of saturated aqueous sodium bicarbonate solution. The phases were separated, and the aqueous phase was extracted three more times with in each case about 10 ml of dichloromethane. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. The product was isolated from the residue by preparative RP-HPLC (mobile phase methanol/water). This gave 283 mg of the target product (78% of theory).
Reaction SMILES: I([O-])(=O)(=O)=O.[Na+].[C:7]([CH:15]([C:28]1[O:29][CH:30]=CC=1)[CH2:16][C:17]([C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[Br:27])([CH3:19])[CH3:18])(=[O:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[O-:33]S([O-])=O.[Na+].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O.CI.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C(#N)C.ClC(Cl)(Cl)Cl.C(#N)C.CC(OC)(C)C.O.[Ru](=O)=O>[CH3:30][O:29][C:28](=[O:33])[CH:15]([C:7](=[O:14])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH2:16][C:17]([C:20]1[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=1[Br:27])([CH3:18])[CH3:19]
Reactant: O=S([O-])[O-]
Reactant: CC(C)(CC(C(=O)c1ccccc1)c1ccco1)c1cc(F)ccc1Br
Agent: O=[Ru]=O
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=C([O-])[O-]
Solvent: CC#N
Solvent: ClC(Cl)(Cl)Cl
Solvent: O
Product: COC(=O)C(CC(C)(C)c1cc(F)ccc1Br)C(=O)c1ccccc1
Reaction time: 0.17 h

Procedure:
A suspension of 10.9 g (50.8 mmol) of sodium periodate in 140 ml of water-acetonitrile-tetrachloromethane (4:2:1) is mixed with 45 mg (0.34 mmol) of ruthenium(IV)oxide-hydrate. After 10 minutes, a solution of 2-[1-benzoyl-3-(2-bromo-5-fluorophenyl)-3-methylbutyl]furan in 40 ml of acetonitrile is added to it, it is stirred for another 10 minutes, and the batch is poured into 400 ml of saturated Na2SO3. A pH of 5 is set with 10% citric acid, and the batch is extracted with ethyl acetate. The combined extracts are dried (Na2SO4) and concentrated by evaporation in a vacuum. The residue is taken up in 8 ml of DMF and treated with 0.42 ml (6.8 mmol) of methyl iodide and 2.21 g (6.8 mmol) of cesium carbonate. After 5 hours at room temperature, the batch is diluted with 600 ml of MTBE, washed with 10% sulfuric acid and saturated NaCl, dried (Na2SO4) and concentrated by evaporation in a vacuum. Column chromatography on silica gel with hexane-ethyl acetate yields 0.9 g of product.
Reaction SMILES: Cl.[NH2:2][NH:3][C:4]([NH2:6])=[O:5].C(N(CC)CC)C.[CH:14]1([C:17](Cl)=O)[CH2:16][CH2:15]1.[OH-].[Na+].Cl>C(Cl)Cl.O>[CH:14]1([C:17]2[NH:6][C:4](=[O:5])[NH:3][N:2]=2)[CH2:16][CH2:15]1
Reactant: O=C(Cl)C1CC1
Reactant: NNC(N)=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: O=c1[nH]nc(C2CC2)[nH]1
Temperature: -10 °C
Reaction time: 0.5 h
Yield: 32.5 %

Procedure:
To a suspension of semicarbazide hydrochloride (5.00 g, 44.8 mmol) in DCM (100 mL) was added triethylamine (10.00 g, 99 mmol) and the mixture was stirred at −10° C. for 30 min. Cyclopropane carbonylchloride (5.00 g, 47.8 mmol) was added at the same temp and the mixture was stirred to RT over night. The solvent from the reaction mixture was completely removed and the residue stirred in MeCN (200 mL) for 1 h. The solids were collected by filtration, washed and dried. The solid was transferred to a RB flask and treated with sodium hydroxide (7.00 g, 175 mmol) and water (20 mL). The resulting reaction mixture was heated at 100° C. for 2 hours. The reaction mixture was cooled and acidified with conc. HCl. The solids were collected by filtration, washed and dried to provide 3-cyclopropyl-1H-1,2,4-triazol-5(4H)-one (1.82 g, 30.4% yield) as white solid. 1H NMR (400 MHz, DMSO-d6): δ11.03 (br s, 2H), 1.67 (m, 1H), 0.82 (m, 2H), 0.73 (m, 2H); MS (ESI) m/z: 126.1 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:16][CH2:15]3)[NH:11][N:10]=2)[C:5]([CH2:17][OH:18])=[CH:4][N:3]=1.N1C=CN=C1.[CH3:24][C:25]([Si:28](Cl)([CH3:30])[CH3:29])([CH3:27])[CH3:26].O>C(Cl)Cl>[Si:28]([O:18][CH2:17][C:5]1[C:6]([NH:8][C:9]2[CH:13]=[C:12]([CH:14]3[CH2:15][CH2:16]3)[NH:11][N:10]=2)=[N:7][C:2]([Cl:1])=[N:3][CH:4]=1)([C:25]([CH3:27])([CH3:26])[CH3:24])([CH3:30])[CH3:29]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCc1cnc(Cl)nc1Nc1cc(C2CC2)[nH]n1
Agent: c1c[nH]cn1
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCc1cnc(Cl)nc1Nc1cc(C2CC2)[nH]n1
Temperature: 20 °C
Reaction time: 16 h
Yield: 99.7 %

Procedure:
A mixture of (2-chloro-4-(5-cyclopropyl-1H-pyrazol-3-ylamino)pyrimidin-5-yl)methanol (350 mg, 1.32 mmol), imidazole (107.6 mg, 1.58 mmol, 1.2 eq), TBDMSCl (238 mg, 1.58 mmol, 1.2 eq) in CH2Cl2 (10 mL) was stirred at 20° C. for 16 h. Water (30 mL) was added and the reaction was extracted with CH2Cl2 (4×30 mL). The combined organic phases were washed (brine), dried (Na2SO4), filtered and concentrated to afford 5-((tert-butyldimethylsilyloxy)methyl)-2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (500 mg, 99%). LC-MS (m/z)=380.0 [M+H]+.
Reaction SMILES: NC1C=CC(C2N(C)C(C#N)=CC=2)=CC=1C(O)(C)C.C1N=CN(C(N2C=NC=C2)=[S:26])C=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:44][C:45]1([CH3:63])[C:50]2[CH:51]=[C:52]([N:55]3[CH:59]=[CH:58][CH:57]=[C:56]3[C:60]#[N:61])[CH:53]=[CH:54][C:49]=2[NH:48][C:47](=O)[O:46]1>C1COCC1>[CH3:44][C:45]1([CH3:63])[C:50]2[CH:51]=[C:52]([N:55]3[CH:59]=[CH:58][CH:57]=[C:56]3[C:60]#[N:61])[CH:53]=[CH:54][C:49]=2[NH:48][C:47](=[S:26])[O:46]1
Reactant: CC1(C)OC(=O)Nc2ccc(-n3cccc3C#N)cc21
Reactant: S=C(n1ccnc1)n1ccnc1
Agent: Cn1c(C#N)ccc1-c1ccc(N)c(C(C)(C)O)c1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CC1(C)OC(=S)Nc2ccc(-n3cccc3C#N)cc21

Procedure:
5-[4-amino-3-(1-hydroxy-1-methyl-ethyl)-phenyl]-1-methyl-1H-pyrrole-2-carbonitrile prepared according to Example 2 is dissolved in THF and TCDI or CDI is added. Extraction using an aqueous dilute hydrochloride solution gives an about quantitative yield of (4,4-dimethyl-2-thioxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile and (4,4-dimethyl-2-oxo-1,4-dihydro-2H-3,1-benzoxazin-6-yl)-1H-pyrrole-2-carbonitrile, respectively.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:21])([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]([OH:24])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:26][CH2:27][C:28](=[O:37])[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>CN(C1C=CN=CC=1)C.CN(C=O)C.CCOCC>[CH2:1]([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:20])([CH3:21])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]([NH:26][CH2:27][C:28](=[O:37])[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=1)=[O:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC1(C)OCCn2c1nc(C(=O)O)c(OCc1ccccc1)c2=O
Reactant: NCC(=O)Cc1ccc(F)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC1(C)OCCn2c1nc(C(=O)NCC(=O)Cc1ccc(F)cc1)c(OCc1ccccc1)c2=O
Reaction time: 4 h
Yield: 78 %

Procedure:
A mixture of 3-(benzyloxy)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxylic acid (prepared according to the procedure in Naidu, B. N. et al WO2005118593) (0.495 g, 1.5 mmol), 1-amino-3-(4-fluorophenyl)propan-2-one hydrochloride (prepared according to the procedure in Maeda, S. et al Chem. Pharm. Bull. 1984, 32, 2536-2543; 0.406 g, 2 mmol), HATU (0.760 g, 2 mmol), Et3N (0.56 mL, 4 mmol) and DMAP (60 mg) in DMF (15 mL) was stirred at room temperature. After 4 h, the reaction mixture was diluted with Et2O (100 mL), washed with water (3×10 mL), brine (10 mL), dried (Na2SO4), filtered and concentrated to give the title compound (0.57 g, 78% yield) as a viscous yellow oil which was used in the subsequent step without purification. 1HNMR (500 MHz, CDCl3) δ: 8.10-8.07 (1H, br s), 7.56 (2H, d, J=7.3 Hz), 7.34-7.28 (3H, m), 7.19 (2H, dd, J=8.6, 5.5 Hz), 7.03 (2H, t, J=8.6 Hz), 5.29 (2H, s), 4.30 (2H, d, J=4.9 Hz), 4.04-3.98 (4H, m), 3.75 (2H, s), 2.79 (6H, s), 1.62 (6H, s). HRMS (M+H) calcd for C26H27N3O5F: 480.1935. found: 480.1930.
Reaction SMILES: [C:1]([O:5][C:6](=[O:21])[N:7]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1I)[CH2:8][CH2:9][S:10]([CH3:13])(=[O:12])=[O:11])([CH3:4])([CH3:3])[CH3:2].[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O>>[C:1]([O:5][C:6](=[O:21])[N:7]([C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[Cl:22])[CH2:8][CH2:9][S:10]([CH3:13])(=[O:12])=[O:11])([CH3:4])([CH3:3])[CH3:2]
Reactant: OB(O)c1ccccc1Cl
Reactant: CC(C)(C)OC(=O)N(CCS(C)(=O)=O)c1cnccc1I
Product: CC(C)(C)OC(=O)N(CCS(C)(=O)=O)c1cnccc1-c1ccccc1Cl

Procedure:
The title compound was prepared in analogy to example 72, from (4-iodo-pyridin-3-yl)-(2-methanesulfonyl-ethyl)-carbamic acid tert-butyl ester and 2-chlorophenylboronic acid (CAS RN 1679-18-1). The product was purified by preparative HPLC (phenomenex gemini column) with a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2). Light brown foam (67%). MS (ESI): m/z=411.11 [M+H]+.
Reaction SMILES: [OH-].[K+].[NH:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[CH:4]1.[NH2:12]OS(O)(=O)=O>O.C(O)C>[NH2:12][N:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[N:5]=[CH:4]1
Reactant: NOS(=O)(=O)O
Reactant: c1ccc2[nH]cnc2c1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Nn1cnc2ccccc21
Temperature: 30 °C
Reaction time: 18 h

Procedure:
In a mixed slovent of water(50 ml) and ethanol(50 ml) was dissolved 19.64 g(35 mmol) of potassium hydroxide and 5.91 g(5 mmol) of 1H-benzimidazole was added thereto. Water(10 ml) containing 14.41 g (125 mmol) of hydroxylamine-O-sulfonic acid was slowly added while maintaining the temperature at 30° C. and the mixture was stirred at the same temperature for 18 hours.
Reaction SMILES: O[C:2]1([CH3:11])[CH:6]([CH2:7][CH:8]=[CH2:9])[C:5](=[O:10])[CH:4]=[CH:3]1.[OH-:12].[Na+].[Na+].[Cl-]>O>[CH2:7]([C:6]1[C:5](=[O:10])[CH2:4][CH:3]([OH:12])[C:2]=1[CH3:11])[CH:8]=[CH2:9]
Reactant: C=CCC1C(=O)C=CC1(C)O
Reactant: [OH-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: C=CCC1=C(C)C(O)CC1=O
Reaction time: 4 h

Procedure:
Into a reaction vessel, a solution of 4-hydroxy-4-methyl-5-allyl-2-cyclopentenone (3 g) and MgCl2.6H2O (4.0 g) in water (120 ml) was charged, and the temperature was elevated up to 100° C. The contents were adjusted to pH 7.3 with 0.1 N NaOH solution, and stirring was continued at 100° C. for 4 hours, during which the pH was maintained at 7.0 to 7.3. After cooling, NaCl (40 g) was added to the reaction mixture, and the resultant mixture was extracted with ether (120 ml) 4 times. The extracts were combined together, dried over anhydrous magnesium sulfate and concentrated at 40° C. under reduced pressure to give an oily substance (2.7 g). The oily substance was chromatographed with silica gel (30 g), followed by development with a solvent mixture of ethyl acetate and hexane (1:2 by volume) to give 2-allyl-3-methyl-4-hydroxy-2-cyclopentenone (2.6 g). Yield, 87%. N.M.R. (CDCl3, internal standard TMS, δ ppm, 90 MHz): 5.71 (complex m, 1H, --CH2 --CH=CHaHb); 5.06 (m, 1H, --CH2 --CH=CHaHb); 4.93 (m, 1H, --CH2 --CH=CHaHb); 4.74 (broad d, 1H, 4-H); 3.94 (broad s, 1H, 4-OH); 2.96 (d, 2H, --CH2 --CHCHaHb); 2.85 (d of d, 1H, 5-H); 2.27 (d of d, 1H, 5-H); 2.11 (s, 3H, 3-CH3).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[S:10])=[CH:4][CH:3]=1.[NH3:11]>CCOCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([NH2:11])=[S:10])=[CH:4][CH:3]=1
Reactant: S=C=Nc1ccc(Cl)cc1
Reactant: N
Solvent: CCOCC
Product: NC(=S)Nc1ccc(Cl)cc1
Reaction time: 18 h

Procedure:
A stirred solution of 4-chlorophenyl isothiocyanate (10.0 g, 0.077 mol) in 100 ml ether was saturated with ammonia gas for five minutes. The reaction mixture was then stirred for 18 hr. The white solid which precipitated was collected by filtration and yielded 6.3 g of N-(4-chlorophenyl)thiourea, M.P. 147-148° C.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:15]#[CH:16])=[N:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[CH:7]=1.I[C:18]1[CH:27]=[CH:26][C:21]([O:22][CH2:23][CH2:24][OH:25])=[CH:20][CH:19]=1>>[Cl:1][C:2]1[C:3]([C:15]#[C:16][C:18]2[CH:27]=[CH:26][C:21]([O:22][CH2:23][CH2:24][OH:25])=[CH:20][CH:19]=2)=[N:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[CH:7]=1
Reactant: C#Cc1ncc(-c2ccc(Cl)cc2)cc1Cl
Reactant: OCCOc1ccc(I)cc1
Product: OCCOc1ccc(C#Cc2ncc(-c3ccc(Cl)cc3)cc2Cl)cc1

Procedure:
The product was prepared analogously to Example 7.1e starting from 3-chloro-5-(4-chlorophenyl)-2-ethynylpyridine and 2-(4-iodophenoxy)ethanol. Yield: 0.48 g (66% of theoretical); C21H15Cl2NO2 (M=384.255); calc.: molpeak (M+H)+384/386/388 (2Cl); found: molpeak (M+H)+: 384/386/388 (2Cl); HPLC-MS: 6.24 minutes (method B).
Reaction SMILES: Cl.[Cl:2][C:3]1[C:11]2[C:6]([N:7]([CH2:12][C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[O:14])[CH:8]=[CH:9][CH:10]=2)=[N:5][C:4]=1[CH3:21].[BH4-].[Na+]>CO>[Cl:2][C:3]1[C:11]2[C:6]([N:7]([CH2:12][CH:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[OH:14])[CH:8]=[CH:9][CH:10]=2)=[N:5][C:4]=1[CH3:21]
Reactant: Cc1nc2n(CC(=O)c3ccccc3)cccc-2c1Cl
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: Cc1nc2n(CC(O)c3ccccc3)cccc-2c1Cl
Temperature: 25 °C
Reaction time: 20 h
Yield: 18.9 %

Procedure:
To a solution of 120 mg (0,37 mmol) of 3-chloro-2-metyl-7-phenacylpyrrolo[2,3-b]pyridine hydrochlorid in 2 ml methanol was added 30 mg (0,79mmol) of sodium borohydride. The mixture was stirred for 20 h at room temperature. The solvent was evaporated and the residue was partitioned between 2 ml of 0,2M hydrochloric acid and 2 ml of ethyl acetate. The aqueos layer was basified by addition of 2M sodium hydroxide and extracted twice with 2 ml of methylene chloride. The combined organic phase was dried over sodium sulfate and the solvent was evaporated. The residue was treated with acetonitrile and the precipitate was filtered off to give 20 mg (19%) 3-chloro-2-methyl-7-(2-phenyl-2-hydroxyethyl)pyrrolo-[2,3-b]pyridine.
Reaction SMILES: O1C2C=CC=CC=2C=C1C1CCCOC1[N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25]([NH:27][CH:28]([CH3:30])[CH3:29])=[O:26])=[CH:22][CH:23]=2)[CH:18]=[N:17]1.Cl.O1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>>[O:35]1[C:36]2[CH:37]=[CH:18][CH:19]=[CH:20][C:21]=2[CH:33]=[C:34]1[C:18]1[C:19]2[C:24](=[CH:23][CH:22]=[C:21]([C:25]([NH:27][CH:28]([CH3:29])[CH3:30])=[O:26])[CH:20]=2)[NH:16][N:17]=1
Reactant: C1COCCO1
Reactant: CC(C)NC(=O)c1ccc2c(cnn2C2OCCCC2c2cc3ccccc3o2)c1
Agent: Cl
Product: CC(C)NC(=O)c1ccc2[nH]nc(-c3cc4ccccc4o3)c2c1
Reaction time: 8 h
Yield: 7 %

Procedure:
(3-Benzo[d]furan-2-yl-1-perhydro-2H-pyran-2-yl(1H-indazol-5-yl))-N -(methylethyl)carboxamide (170 mg, 0.41 mmol) was taken up in a solution of 4 N HCl in dioxane and allowed to stir overnight. The reaction was neutralized to pH 7 and extracted with ethyl acetate. The organic layer was dried, filtered, and concentrated to yield the crude material which was purified by semi-preprative HPLC to yield the title compound (9 mg, 7% yield). 1H NMR (DMSO-d6) δ 13.8 (s, 1H), 8.7 (s, 1H), 8.4 (d, 1H), 8.0 (d, 1H), 7.6–7.8 (m, 4H), 7.4 (m, 2H), 4.2 (m, 1H), 3.2 (d, 1H), 1.2 (d, 6H)
Reaction SMILES: [CH3:1][CH:2]([CH3:24])[CH2:3][CH:4]([C:8]1[CH:9]=[C:10](C2C=CC=CC=2)[CH:11]=[C:12](C(F)(F)F)[CH:13]=1)[C:5]([OH:7])=[O:6].[F:25][C:26]([F:39])([F:38])[C:27]1[CH:32]=[CH:31][C:30](/[CH:33]=[CH:34]/B(O)O)=[CH:29][CH:28]=1>>[CH3:24][CH:2]([CH3:1])[CH2:3][CH:4]([C:8]1[CH:9]=[C:10]([C:30]2[CH:31]=[CH:32][C:27]([C:26]([F:39])([F:38])[F:25])=[CH:28][CH:29]=2)[CH:11]=[C:12]([CH:34]=[CH:33][C:30]2[CH:31]=[CH:32][C:27]([C:26]([F:39])([F:38])[F:25])=[CH:28][CH:29]=2)[CH:13]=1)[C:5]([OH:7])=[O:6]
Reactant: OB(O)/C=C/c1ccc(C(F)(F)F)cc1
Reactant: CC(C)CC(C(=O)O)c1cc(-c2ccccc2)cc(C(F)(F)F)c1
Product: CC(C)CC(C(=O)O)c1cc(C=Cc2ccc(C(F)(F)F)cc2)cc(-c2ccc(C(F)(F)F)cc2)c1

Procedure:
The title compound was prepared from a Nigishi coupling of 4-methyl-2-(5-trifluoromethyl-biphenyl-3-yl)pentanoic acid (intermediate compound 1g) with trans-2-(4-trifluoromethylphenyl)-vinyl-boronic acid under the conditions described in Example 14; 1H NMR (400 MHz, MeOD) δ ppm 0.78-0.89 (m, 6 H), 1.47 (dt, J=13.39, 6.63 Hz, 1 H), 1.62 (ddd, J=13.63, 7.09, 6.91 Hz, 1 H), 1.91-1.98 (m, 1 H), 3.68 (t, J=7.83 Hz, 1 H), 7.33 (d, J=16.4 Hz, 1 H), 7.26 (d, J=16.5 Hz, 1 H), 7.48-7.58 (m, 4 H), 7.64-7.70 (m, 5 H), 7.75-7.78 (m, 2 H).