Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[O:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH:26]1[O:31][CH2:32][CH2:33][C:34]([OH:36])=O.C(N(C(C)C)C(C)C)C.[C:46]([C:50]1[O:54][C:53]([C:55]2[C:56]([NH2:73])=[N:57][CH:58]=[C:59]([C:61]3[N:65]([CH3:66])[N:64]=[C:63]([CH:67]4[CH2:72][CH2:71][NH:70][CH2:69][CH2:68]4)[N:62]=3)[N:60]=2)=[N:52][N:51]=1)([CH3:49])([CH3:48])[CH3:47]>C(#N)C>[NH2:73][C:56]1[N:57]=[CH:58][C:59]([C:61]2[N:65]([CH3:66])[N:64]=[C:63]([CH:67]3[CH2:72][CH2:71][N:70]([C:34](=[O:36])[CH2:33][CH2:32][O:31][CH:26]4[CH2:27][CH2:28][CH2:29][CH2:30][O:25]4)[CH2:69][CH2:68]3)[N:62]=2)=[N:60][C:55]=1[C:53]1[O:54][C:50]([C:46]([CH3:49])([CH3:47])[CH3:48])=[N:51][N:52]=1
Reactant: Cn1nc(C2CCNCC2)nc1-c1cnc(N)c(-c2nnc(C(C)(C)C)o2)n1
Reactant: O=C(O)CCOC1CCCCO1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: Cn1nc(C2CCN(C(=O)CCOC3CCCCO3)CC2)nc1-c1cnc(N)c(-c2nnc(C(C)(C)C)o2)n1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 89.1 %

Procedure:
O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (30.4 g, 80.04 mmol), was added portionwise to a stirred solution of 3-(tetrahydro-2H-pyran-2-yloxy)propanoic acid (12.67 g, 72.76 mmol) and N-ethyl-N-isopropylpropan-2-amine (25.3 mL, 145.52 mmol) dissolved in acetonitrile (200 mL) at 25° C. The resulting solution was stirred at 25° C. for 20 minutes then 3-(5-tert-butyl-1,3,4-oxadiazol-2-yl)-5-(1-methyl-3-(piperidin-4-yl)-1H-1,2,4-triazol-5-yl)pyrazin-2-amine (30 g, 72.76 mmol) was added portionwise, washing the last portion into the mixture as a slurry in acetonitrile (100 mL). After stirring for 1 hour the precipitate was collected by filtration, washed with acetonitrile and drying in vacuo to afford 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-methyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one (35.0 g, 89%) as a beige solid. The filtrate was diluted with DCM (600 mL), washed with water, dried over magnesium sulfate and concentrated. The residue was purified by flash chromatography on silica gel eluting with a gradient of 2 to 2.5% 7N ammonia in methanol with dichloromethane. A second crop of product (3.31 g, 6.13 mmol, 8.43%) was also obtained as a cream solid. Both samples were combined to give a beige solid: 1H NMR Spectrum: (DMSO-d6) 1.44 (9H, s), 1.52-1.79 (4H, m), 1.88-2.04 (2H, m), 2.53-2.73 (2H, m), 2.73-2.87 (1H, m), 2.91-3.05 (1H, m), 3.13-3.24 (1H, m), 3.37-3.47 (1H, m), 3.53-3.65 (1H, m), 3.7-3.8 (1H, m), 3.81-3.89 (1H, m), 3.89-3.99 (1H, m), 4.20 (3H, s), 4.29-4.4 (1H, m), 4.54-4.61 (1H, m), 7.60-8.20 (2H, br), 8.85 (1H, s); Mass Spectrum [M+H]+=540.
Reaction SMILES: Br[CH:2]([CH2:5][CH3:6])[CH2:3][CH3:4].[Mg].[CH:8]([C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:19])[CH3:18])=[CH:12][CH:11]=1)=[O:9].[NH4+].[Cl-]>CCOCC.C1COCC1>[CH2:3]([CH:2]([CH2:5][CH3:6])[CH:8]([C:10]1[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:19])[CH3:18])=[CH:14][CH:15]=1)[OH:9])[CH3:4]
Reactant: CCC(Br)CC
Reactant: CC(=O)Nc1ccc(C=O)cc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCC(CC)C(O)c1ccc(NC(C)=O)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 52.2 %

Procedure:
A solution of 3-bromopentane (0.331 mol) in (C2H5)2O (200 ml) was added dropwise to a solution of magnesium turnings (0.331 mol) in (C2H5)2O, the mixture was stirred at RT for 2 hours and then cooled to 0° C. A solution of N-(4-formylphenyl)acetamide (0.11 mol) in THF (400 ml) was added dropwise and the mixture was stirred for 10 minutes. The mixture was poured into aqueous NH4Cl and extracted with EtOAc. The organic layer was dried, filtered off and the solvent evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 97/3/0.1). The pure fractions were collected and evaporated, yielding 13.5 g (52%) of (±)-N-[4-(2-ethyl-1-hydroxybutyl)phenyl]acetamide (interm. 13).
Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C@:17]3([CH3:23])[CH2:21][O:20][C:19](=[O:22])[NH:18]3)[CH:13]=2)[CH:8]=1)(=O)=O.[CH2:26]([O:33][C:34]1[CH:35]=[C:36]([SH:40])[CH:37]=[CH:38][CH:39]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O1CCOCC1.C(N(CC)C(C)C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:26]([O:33][C:34]1[CH:35]=[C:36]([S:40][C:7]2[CH:8]=[C:9]3[C:14](=[CH:15][CH:16]=2)[CH:13]=[C:12]([C@:17]2([CH3:23])[CH2:21][O:20][C:19](=[O:22])[NH:18]2)[CH:11]=[CH:10]3)[CH:37]=[CH:38][CH:39]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: Sc1cccc(OCc2ccccc2)c1
Reactant: C[C@@]1(c2ccc3cc(OS(=O)(=O)C(F)(F)F)ccc3c2)COC(=O)N1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Solvent: CCN(C(C)C)C(C)C
Product: C[C@@]1(c2ccc3cc(Sc4cccc(OCc5ccccc5)c4)ccc3c2)COC(=O)N1
Temperature: 25 °C

Procedure:
(R)-6-(4-methyl-2-oxooxazolidin-4-yl)naphthalen-2-yl trifluoromethanesulfonate (30.0 mg, 0.0000799 mol), 3-benzyloxy-benzenethiol (20.7 mg, 0.0000959 mol), tris(dibenzylideneacetone)dipalladium(0) (8.78 mg, 9.59E-6 mol) and xantphos (11.1 mg, 0.0000192 mol) were dissolved in 1,4-dioxane (3 mL, 0.04 mol, anhydrous), degassed in low vacuum and backfilled with N2 five times. N,N-diisopropylethylamine (0.0418 mL, 0.000240 mol) pre-degassed in the same way was added under N2 atomsphere. The mixture was heated to reflux for 20 hours. The mixture was cooled to room temperature, filtered, evaporated, and the residue was chromatographed with EtOAc/hexane (0:100 to 10:90) to give (R)-4-(6-(3-(benzyloxy)phenylthio)naphthalen-2-yl)-4-methyloxazolidin-2-one as a solid product (30.0 mg, 85%). Rf (EtOAc:hexane=1:9)=0.3.
Reaction SMILES: Cl.[F:2][C:3]1[N:8]=[C:7]([C:9]2[C:10](=[O:16])[NH:11][C:12](=[O:15])[NH:13][CH:14]=2)[CH:6]=[CH:5][CH:4]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:24][CH2:25][CH:26]([O:29][CH3:30])[O:27][CH3:28].O>CN(C=O)C>[CH3:28][O:27][CH:26]([O:29][CH3:30])[CH2:25][CH2:24][N:13]1[CH:14]=[C:9]([C:7]2[CH:6]=[CH:5][CH:4]=[C:3]([F:2])[N:8]=2)[C:10](=[O:16])[NH:11][C:12]1=[O:15]
Reactant: O=c1[nH]cc(-c2cccc(F)n2)c(=O)[nH]1
Reactant: COC(CCBr)OC
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(CCn1cc(-c2cccc(F)n2)c(=O)[nH]c1=O)OC
Temperature: 25 °C
Reaction time: 1 h
Yield: 70.6 %

Procedure:
A mixture of 5-(6-Fluoro-pyridin-2-yl)-1H-pyrimidine-2,4-dione hydrochloride (Prep75, 200 mg, 0.82 mmol), and K2CO3 (169 mg, 1.23 mmol) in DMF (4 ml) was stirred 1 hour at room temperature. 3-Bromo-1,1dimethoxy-propane (165 mg, 0.90 mmol) was added and stirring was continued for 48 hours. Water (50 ml) was added and the product was extracted with ethyl acetate. The organic phase was dried (Na2SO4) and evaporated. The crude was triturated with iPr2O to give 179 mg of the final compound as a white solid (70% yield).
Reaction SMILES: [OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([OH:11])[CH:5]=[CH:4][C:3]=1[C:12](=[O:14])[CH3:13].O[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]([O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)[C:24]2[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=2)[C:27]#[N:28])=[CH:19][CH:18]=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>ClCCl.C1(C)C=CC=CC=1>[C:12]([C:3]1[CH:4]=[CH:5][C:6]([O:11][CH2:16][C:17]2[CH:18]=[CH:19][C:20]([CH:23]([O:32][CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][O:34]3)[C:24]3[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=3)[C:27]#[N:28])=[CH:21][CH:22]=2)=[C:7]([CH2:8][CH2:9][CH3:10])[C:2]=1[OH:1])(=[O:14])[CH3:13]
Reactant: N#Cc1cccc(C(OC2CCCCO2)c2ccc(CO)cc2)c1
Reactant: CCCc1c(O)ccc(C(C)=O)c1O
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: CCCc1c(OCc2ccc(C(OC3CCCCO3)c3cccc(C#N)c3)cc2)ccc(C(C)=O)c1O
Temperature: 25 °C
Reaction time: 8 h
Yield: 66.7 %

Procedure:
Stir a solution of 1-(2,4-dihydroxy-3-propyl-phenyl)-ethanone (1.75 g, 9 mmol), 3-[(4-hydroxymethyl-phenyl)-(tetrahydro-pyran-2-yloxy)-methyl]-benzonitrile (2.9 g, 9 mmol), toluene (10 mL), and dichloromethane (10 mL) at −20° C. Add 1,1′-(azodicarbonyl)dipiperidine (4.5 g, 18 mmol) followed by tributylphosphine (4.5 mL, 18 mmol) and allow the resulting yellow solution to stir at room temperature overnight. Concentrate the resulting thick reaction mixture and dilute with ether (50 mL). Cool the slurry to 0° C. with stirring, for 30 minutes. Filter the reaction mixture, concentrate, and purify via silica chromatography eluting with 1:1 hexanes:(5:4:1 hexanes:dichloromethane:ethyl acetate) to give the title compound (3 g, 67%), as an orange thick oil. LCMS (m/z) 498 M−1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[C:4]([F:9])[C:3]=1[CH:10]([C:16]([O:18]CC)=O)[C:11]([O:13]CC)=O.[NH2:21][C:22]1[NH:23][CH:24]=[CH:25][N:26]=1.C(N(CCCC)CCCC)CCC>C(OCC)(=O)C>[F:9][C:4]1[CH:5]=[C:6]([F:8])[CH:7]=[C:2]([F:1])[C:3]=1[C:10]1[C:11]([OH:13])=[N:21][C:22]2[N:23]([CH:24]=[CH:25][N:26]=2)[C:16]=1[OH:18]
Reactant: CCOC(=O)C(C(=O)OCC)c1c(F)cc(F)cc1F
Reactant: Nc1ncc[nH]1
Solvent: CCCCN(CCCC)CCCC
Solvent: CCOC(C)=O
Product: Oc1nc2nccn2c(O)c1-c1c(F)cc(F)cc1F
Temperature: 25 °C

Procedure:
A mixture of diethyl 2-(2,4,6-trifluorophenyl)malonate (U.S. Pat. No. 6,156,925) (870 mg, 3.0 mmol), 2-aminoimidazole (Hel. Acta. Chim. 76, 2066 (1993)) (274 mg, 3.3 mmol), and 1.0 mL of tributylamine is stirred under nitrogen atmosphere at 160° C. for 0.5 h and cooled to room temperature. The mixture is dissolved in ethyl acetate and the organic layer is washed with 1.0 N hydrochloric acide (×3) and saturated sodium chloride, dried over magnesium sulfate, and concentrated. The residue is dissolved in ethyl acetate (5 mL) and to this solution is added hexanes (50 mL). The precipitates are collected by filtration, washed with hexanes to give 6-(2,4,6-trifluorophenyl)imidazo[1,2-a]pyrimidine-5,7-diol as a tan solid (180 mg). MS: m/z 279.9(M−H).
Reaction SMILES: [C:1]1([Li])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:8]1([CH2:14][C@H:15]2[C@H:19]([C:20](OC)=[O:21])[O:18][C:17]([CH3:25])([CH3:24])[N:16]2[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1.[Cl-].[NH4+]>CCOCC>[C:20]([C@@H:19]1[O:18][C:17]([CH3:24])([CH3:25])[N:16]([C:26]([O:28][C:29]([CH3:32])([CH3:30])[CH3:31])=[O:27])[C@H:15]1[CH2:14][CH:8]1[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1)(=[O:21])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: COC(=O)[C@@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1CC1CCCCC1
Reactant: [Li]c1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Product: CC(C)(C)OC(=O)N1[C@@H](CC2CCCCC2)[C@H](C(=O)c2ccccc2)OC1(C)C
Reaction time: 0.5 h

Procedure:
2.36 ml (2 mmol) of a 0.76N solution of phenyllithium in ether are sprayed at -75° into 355 mg (1 mmol) of 3-t-butyl 5-methyl (4S,5R)-4-(cyclohexylmethyl)-2,2-dimethyl-3,5-oxazolidinedicarboxylate in 20 ml of ether and the reaction mixture is stirred at this temperature for 30 minutes, subsequently poured into 50 ml of saturated ammonium chloride solution and extracted three times with 150 ml of ether each time. The three ether extracts are washed in succession with in each case 70 ml of 2N sodium bicarbonate solution and 70 ml of saturated sodium chloride solution, combined, dried over magnesium sulphate, filtered and evaporated. The residual oil (540 mg) is chromatographed on 30 g of silica gel with a 98:2 mixture of toluene and ethyl acetate as the eluting agent, whereby there are obtained 300 mg of t-butyl (4S,5R)-5-benzoyl-4-(cyclohexylmethyl)-2,2-dimethyl-3-oxazolidinecarboxylate as a white solid, MS: 401 (M)+.
Reaction SMILES: C(O)(=O)C.[CH2:5]([C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[C:20]([C:25]1[CH:30]=[CH:29][C:28]([O:31]C)=[CH:27][CH:26]=1)[CH:19]=[CH:18]2)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].Br>O>[CH2:5]([C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[C:20]([C:25]1[CH:30]=[CH:29][C:28]([OH:31])=[CH:27][CH:26]=1)[CH:19]=[CH:18]2)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCc1ccc2nc(-c3ccc(OC)cc3)ccc2c1
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: CCCCCCCCCCc1ccc2nc(-c3ccc(O)cc3)ccc2c1
Temperature: 100 °C
Reaction time: 12 h
Yield: 70.6 %

Procedure:
To 35 ml of acetic acid, 2.5 g of 6-decyl-2-(4-methoxyphenyl)quinoline and 15 ml of 47%-hydrobromic acid were added, followed by stirring for 12 hours at 100° C. and further stirring overnight at room temperature. After the reaction, the reaction mixture was poured into water and subjected to extraction with chloroform. The organic layer was washed with water and dried with anhydrous sodium sulfate, followed by distilling-off of the solvent and purification by silica gel column chromatography to obtain 1.7 g of 6-decyl-2-(4-hydroxyphenyl)quinoline.
Reaction SMILES: [C:1]1([N:7]2[CH2:11][CH2:10][C:9]([NH2:12])=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>CN(C)C=O.O1CCOCC1>[C:1]1([N:7]2[CH:11]=[CH:10][C:9]([NH2:12])=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NC1=NN(c2ccccc2)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: C1COCCO1
Product: Nc1ccn(-c2ccccc2)n1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 24.7 %

Procedure:
To a solution of 1-phenyl-4,5-dihydro-1H-pyrazol-3-ylamine (50.0 g) in N,N-dimethylformamide (150 ml) and 1,4-dioxane (500 ml) was added 3,4,5,6-tetrachloro-1,4-benzoquinone (84.0 g) under ice-cooling over 20 minutes, and the mixture was stirred at room temperature for 4.5 hours. To the reaction mixture was added a 2M aqueous solution of sodium hydroxide (400 ml) under ice-cooling over 25 minutes, and the mixture was stirred at room temperature for 1 hour. The mixture was filtered through Celite to remove the insoluble substance, and eluted with ethyl acetate (250 ml×3), and then the filtrate was extracted with ethyl acetate (300 ml). The resulting organic layer was sequentially washed with water (300 ml) and a saturated aqueous solution of sodium chloride (300 ml). The separated aqueous layer was extracted twice with ethyl acetate (300 ml). To the combined organic layer were added anhydrous sodium sulfate (50 g) and silica gel (50 g), and the mixture was stirred at room temperature for 1 hour. This mixture was filtered with silica gel (100 g) on Celite, and subjected to elution with ethyl acetate (250 ml×3). The filtrate was concentrated, and diisopropyl ether (500 ml) was added to the resulting residue, and the mixture was stirred at room temperature. The insoluble substance was collected by filtration, washed twice with diisopropyl ether (100 ml), and dried under reduced pressure to give the titled compound (12.2 g).
Reaction SMILES: C([CH:4]([C:10](=[O:19])[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH3:18])[C:5]([O:7][CH2:8][CH3:9])=[O:6])(=O)C.C(O)C.[O-]CC.[Na+]>O>[CH3:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][C:10](=[O:19])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6]
Reactant: CCOC(=O)C(C(C)=O)C(=O)Cc1ccccc1C
Agent: CC[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCOC(=O)CC(=O)Cc1ccccc1C

Procedure:
Following the method of Hunsdiecker [Berichte, 75, 454 (1942)], 26 parts of ethyl 2-acetyl-4-(2-methylphenyl)-3-oxobutanoate was stirred for 10 hours at room temperature with 100 parts ethanol and 6.8 parts of sodium ethoxide. The mixture was diluted with water and extracted with ether. The solvent was then evaporated to give ethyl 4-(2-methylphenyl)-3-oxobutanoate.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:12]=[N:13][N:14]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=4)[CH:15]=3)=[CH:9][N:8]([S:24]([C:27]3[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[C:5]2=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:42]2[CH:47]=[CH:46][C:45]([NH:48][CH:49]3[CH2:54][CH2:53][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:51][CH2:50]3)=[CH:44][CH:43]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.O.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:23][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][CH:20]=1)[CH2:16][N:14]1[CH:15]=[C:11]([C:10]2[C:4]3[C:5](=[N:6][CH:7]=[C:2]([C:42]4[CH:43]=[CH:44][C:45]([NH:48][CH:49]5[CH2:50][CH2:51][N:52]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:53][CH2:54]5)=[CH:46][CH:47]=4)[CH:3]=3)[N:8]([S:24]([C:27]3[CH:28]=[CH:29][C:30]([CH3:31])=[CH:32][CH:33]=3)(=[O:25])=[O:26])[CH:9]=2)[CH:12]=[N:13]1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(F)c4)c3)c3cc(Br)cnc32)cc1
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: Cc1ccc(S(=O)(=O)n2cc(-c3cnn(Cc4cccc(F)c4)c3)c3cc(-c4ccc(NC5CCN(C(=O)OC(C)(C)C)CC5)cc4)cnc32)cc1
Yield: 63.4 %

Procedure:
Using similar reaction conditions as described in step-ii of example-1, 5-bromo-3-(1-(3-fluorobenzyl)-1H-pyrazol-4-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (compound of Step-i of example 9) (150 mg, 0.280 mmol) was coupled with tert-butyl 4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)amino)piperidine-1-carboxylate (Intermediate 68)(137 mg, 0.34 mmol) using sodium carbonate (79 mg, 0.75 mmol) and Pd(PPh3)2Cl2 (10 mg, 0.014 mmol) in DME/water (20/2 mL). This afforded 130 mg (63.4% yield) after purification by column (Silica gel 6/120) using 50% EtOAc/DCM as eluent. MS: m/z=720.8 (M+1).
Reaction SMILES: [F:1][C:2]([F:14])([C:7]1[CH:11]=[CH:10][N:9]([CH2:12]O)[N:8]=1)[C:3]([F:6])([F:5])[F:4].S(Cl)([Cl:17])=O>ClCCl>[Cl:17][CH2:12][N:9]1[CH:10]=[CH:11][C:7]([C:2]([F:14])([F:1])[C:3]([F:6])([F:5])[F:4])=[N:8]1
Reactant: OCn1ccc(C(F)(F)C(F)(F)F)n1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: FC(F)(F)C(F)(F)c1ccn(CCl)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1.98 g of 3-(pentafluoroethyl)-1H-pyrazole-1-ylmethanol was dissolved to 20 ml of dichloromethane. 1.5 ml of thionyl chloride was added to the solution, followed by stirring at room temperature for overnight. The reaction mixture was concentrated under reduced pressure to obtain 2.01 g of 1-(chloromethyl)-3-(pentafluoroethyl)-1H-pyrazole.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][NH2:12].[CH:13](OCC)=[O:14]>>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][NH:12][CH:13]=[O:14]
Reactant: NCC1COc2ccccc2O1
Reactant: CCOC=O
Product: O=CNCC1COc2ccccc2O1

Procedure:
Racemic 2,3-dihydro-1,4-benzdioxin-2-ylmethylamine (825 mg, 5 mmol) was dissolved in ethyl formate (15 mL), refluxed for 30 min and evaporated in vacuo to yield N-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-formamide as an oil.
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[N:13][C:12]([C:15]3[CH:30]=[CH:29][C:18]([CH2:19][CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:17][CH:16]=3)=[N:11]2)=[CH:6][CH:5]=1.[CH:33]1([CH2:36]Br)[CH2:35][CH2:34]1>>[C:24]([O:23][C:22](=[O:28])[N:21]([CH2:36][CH:33]1[CH2:35][CH2:34]1)[CH2:20][CH2:19][C:18]1[CH:29]=[CH:30][C:15]([C:12]2[N:13]=[CH:14][N:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:31])[F:32])=[CH:9][CH:8]=3)[N:11]=2)=[CH:16][CH:17]=1)([CH3:25])([CH3:26])[CH3:27]
Reactant: BrCC1CC1
Reactant: CC(C)(C)OC(=O)NCCc1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1
Product: CC(C)(C)OC(=O)N(CCc1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1)CC1CC1

Procedure:
The title compound was prepared as described in Example 102 using tert-butyl 4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenethylcarbamate (C50) and cyclopropylmethyl bromide and isolated as a clear oil (0.155 g, 96%): 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1H), 8.16-8.07 (m, 2H), 7.84-7.77 (m, 2H), 7.39 (dq, J=8.0, 0.9 Hz, 2H), 7.31 (s, 2H), 3.50 (t, J=7.6 Hz, 2H), 3.17-2.86 (m, 4H), 1.48 (s, 9H), 0.87 (ddd, J=11.2, 9.0, 6.7 Hz, 1H), 0.49 (d, J=8.0 Hz, 2H), 0.21 (s, 2H); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 503 ([M+H]+).
Reaction SMILES: [I:1][C:2]1[CH:3]=[N:4][N:5]([C@H:7]2[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9][CH2:8]2)[CH:6]=1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].N1C=CN=C1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Si:14]([O:13][C@H:10]1[CH2:9][CH2:8][C@H:7]([N:5]2[CH:6]=[C:2]([I:1])[CH:3]=[N:4]2)[CH2:12][CH2:11]1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]
Reactant: O[C@H]1CC[C@H](n2cc(I)cn2)CC1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)O[C@H]1CC[C@H](n2cc(I)cn2)CC1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
A mixture of trans-4-(4-iodo-1H-pyrazol-1-yl)-cyclohexanol (1.00 g, 3.42 mmol), tert-butyldimethylsilyl chloride (1.03 g, 6.85 mmol), and DMAP (80 mg, 0.7 mmol), 1H-imidazole (699 mg, 10.3 mmol) in DCM (20 mL) was stirred RT for 20 min. The mixture was diluted with DCM and washed with saturated NaHCO3. The organic layer was dry-loaded onto silica gel. Flash chromatography (3% EtOAc:hexanes) afforded 1.37 g (98%) of the title compound as a clear oil. 1H NMR (400 MHz, DMSO-d6): δ 0.05 (s, 6 H), 0.86 (s, 9 H), 1.33-1.47 (m, 2 H), 1.70-1.91 (m, 4 H), 1.96 (d, J=11.9 Hz, 2 H), 3.58-3.75 (m, 1 H), 4.11-4.21 (m, 1 H), 7.49 (s, 1 H), 7.92 (s, 1 H); MS (ESI): 407.05 [M+H]+; HPLC tR=3.22 min.
Reaction SMILES: COC1C=[CH:29][C:6]([CH2:7][NH:8][CH2:9][CH2:10][NH:11][C:12]([C:14]2[S:15][CH:16]=[CH:17][C:18]=2[NH:19][C:20]2[CH:25]=[CH:24][N:23]=[C:22]3[NH:26][CH:27]=[CH:28][C:21]=23)=[O:13])=[CH:5][CH:4]=1.[S:31]1C=CC(C=O)=C1>>[S:31]1[CH:4]=[CH:5][C:6]([CH2:7][NH:8][CH2:9][CH2:10][NH:11][C:12]([C:14]2[S:15][CH:16]=[CH:17][C:18]=2[NH:19][C:20]2[CH:25]=[CH:24][N:23]=[C:22]3[NH:26][CH:27]=[CH:28][C:21]=23)=[O:13])=[CH:29]1
Reactant: O=Cc1ccsc1
Reactant: COc1ccc(CNCCNC(=O)c2sccc2Nc2ccnc3[nH]ccc23)cc1
Product: O=C(NCCNCc1ccsc1)c1sccc1Nc1ccnc2[nH]ccc12

Procedure:
This compound was prepared in an analogous manner as 3-(1H-Pyrrolo[2,3-b]pyridin-4-ylamino)-thiophene-2-carboxylic acid [2-(4-methoxy-benzylamino)-ethyl]amide using 3-thiophenecarboxaldehyde instead of 4-methoxy benzaldehyde. LCMS (ESI) 398 (M+H) 1H NMR (400 MHz, DMSO-d6) δ ppm 11.52 (1H, br. s.) 10.26 (1H, s) 7.98-8.08 (2H, m) 7.77 (1H, d, J=5.42 Hz) 7.46 (1H, d, J=5.42 Hz) 7.42 (1H, dd, J=4.93, 2.98 Hz) 7.30 (1H, dd, J=3.29, 2.66 Hz) 7.24 (1H, dd, J=2.78, 1.03 Hz) 7.05 (1H, dd, J=4.91, 1.20 Hz) 6.80 (1H, d, J=5.42 Hz) 6.43 (1H, dd, J=3.44, 1.93 Hz) 3.67 (2H, s) 3.34 (2H, d, J=5.76 Hz) 2.64 (2H, t, J=6.54 Hz)
Reaction SMILES: [C:1]([C:3]1([OH:13])[CH:10]2[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:12][CH:4]1[CH2:5]3)[CH2:9]2)#[N:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].C1CCCCC1>CCOCC>[NH2:2][CH2:1][C:3]1([OH:13])[CH:4]2[CH2:12][CH:8]3[CH2:7][CH:6]([CH2:11][CH:10]1[CH2:9]3)[CH2:5]2
Reactant: N#CC1(O)C2CC3CC(C2)CC1C3
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: C1CCCCC1
Product: NCC1(O)C2CC3CC(C2)CC1C3
Yield: 75.4 %

Procedure:
A solution of 2-cyanoadamantan-2-ol (6.0 grams, 0.03 mol) in ether was added to a suspension of lithium aluminum hydride (3.9 grams, 0.13 mol) in ether. The reaction mixture was refluxed for 6 hours. Following workup, 4.10 grams of 2-aminomethyl-2-hydroxyadamantane were obtained as white crystals, melting point 154°-156° C. (cyclohexane).