Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28]Cl)=[CH:21][CH:20]=1)[C:13]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH:32][CH:31]=1)=[C:12]2[CH3:44])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[K+].[NH:47]1[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]1.O>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][N:47]3[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48]3)=[CH:21][CH:20]=1)[C:13]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH:32][CH:31]=1)=[C:12]2[CH3:44])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(-c2ccc(OCc3ccccc3)cc2)n(Cc2ccc(OCCCCl)cc2)c2ccc(OCc3ccccc3)cc12
Reactant: C1CCNCC1
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1c(-c2ccc(OCc3ccccc3)cc2)n(Cc2ccc(OCCCN3CCCCC3)cc2)c2ccc(OCc3ccccc3)cc12

Procedure:
A solution of 5-Benzyloxy-2-(4-benzyloxy-phenyl)-1-[4(3-chloro-propoxy)-benzyl]-3-methyl-1H-indole No. 164 (3 g, 5.1 mmol), potassium iodide (2.5 g, 15.3 mmol) and piperidine (3.0 mL, 30.6 mmol) were heated in DMF (30 mL) at 100° C. for 18 hours. The reaction was worked up by pouring into water and extracting with ethyl acetate. The organic layer was washed with water, brine and dried over magnesium sulfate. The solution was concentrated to an oil and the product precipitated out by adding methanol. The product was obtained as a white solid: Mp=104-106° C.; 1H NMR (DMSO) 7.47 (d, 4H, J=7.5 Hz), 7.38 (q, 4H, J=7.9 Hz), 7.36-7.30 (m, 1H), 7.28 (d, 2H, J=8.3 Hz), 7.19 (d, 1H, J=8.8 Hz), 7.12-7.10 (m, 4H), 6.80 (dd, 1H, J=8.8, 2.0 Hz), 6.72 (s, 4H), 5.14 (s, 2H), 5.13 (s, 2H), 5.11 (s, 2H), 3.86 (t, 2H, J=6.4 Hz), 2.35-2.20 (m, 6H), 2.14 (s, 3H), 1.78-1.75 (m, 2H), 1.47-1.42 (m, 4H), 1.40-1.31 (m, 2H); MS eI m/z 650.
Reaction SMILES: [OH:1][CH2:2][C:3]([CH3:8])([CH3:7])[C:4](O)=[O:5].[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][NH:17][OH:18].C1(N=C=NC2CCCCC2)CCCCC1>C(O)C.C(Cl)(Cl)Cl>[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][N:17]([OH:18])[C:4](=[O:5])[C:3]([CH3:8])([CH3:7])[CH2:2][OH:1]
Reactant: CC(C)(CO)C(=O)O
Reactant: ONCc1ccccc1Cl
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCO
Solvent: ClC(Cl)Cl
Product: CC(C)(CO)C(=O)N(O)Cc1ccccc1Cl
Temperature: 25 °C
Reaction time: 60 h
Yield: 7.9 %

Procedure:
To a stirred solution of 3.0 grams (0.025 mole) of 3-hydroxy-2,2-dimethylpropionic acid (Example 12, Step A) and 3.9 grams (0.025 mole) of N-(2-chlorophenyl)methyl hydroxylamine (Example 1, Step A-2) in 65 ml of ethanol was added dropwise a solution of 5.2 grams (0.025 mole) of dicyclohexylcarbodiimide in 25 ml of chloroform. Upon completion of addition the reaction mixture was stirred at ambient temperature for 60 hours. The reaction mixture was concentrated under reduced pressure to give a residual solid. The solid was recrystallized from ethanol, then from ethanol-water to give a solid; mp 229°-230°. The filtrates from the recrystallizations were combined and concentrated under high vacuum to give a residual oil. The residual oil was subjected to column chromatography. Elution was accomplished using 4:1--cyclohexane:ethyl acetate. The appropriate fraction was concentrated under reduced pressure to give a solid. The solid was recrystallized from ethyl acetatehexane to give 0.51 gram of N-[(2-chlorophenyl)methyl]-N,3-dihydroxy-2,2-dimethylpropanamide; mp 130°-132°. The solid was recrystallized a second time from ethyl acetate-cyclohexane to raise the mp to 131°-132°.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:29]([O-])=O)[C:18]([NH:19][C@H:20]4[CH2:25][CH2:24][C@H:23]([CH2:26][O:27][CH3:28])[CH2:22][CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>[Fe].CO.O>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([NH2:29])[C:18]([NH:19][C@H:20]4[CH2:21][CH2:22][C@H:23]([CH2:26][O:27][CH3:28])[CH2:24][CH2:25]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: COC[C@H]1CC[C@H](Nc2c([N+](=O)[O-])cnc3c2ccn3S(=O)(=O)c2ccccc2)CC1
Agent: [Fe]
Solvent: CO
Solvent: O
Product: COC[C@H]1CC[C@H](Nc2c(N)cnc3c2ccn3S(=O)(=O)c2ccccc2)CC1

Procedure:
A mixture of trans (1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-yl)-(4-methoxymethyl-cyclohexyl)-amine (1.92 g, 4.32 mmol), iron powder (0.96 g, 17.3 mmol) ammonium chloride (1.39 g, 26.0 mmol) and methanol/water (90 mL, 3:1) was stirred and heated at reflux for 1 hour. The cooled mixture was filtered through a pad of Celite® washing the filter cake with methanol. The combined filtrate was concentrated to dryness and the residue dissolved in DCM then purified by column chromatography on silica gel (eluting with 20%-50% ethyl acetate in DCM) affording 1.79 g (99%) of trans 1-benzenesulfonyl-N*4*-(4-methoxymethyl-cyclohexyl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine as a grey solid. LCMS (Method I, ESI): RT=2.49 min, m+H=415.2; 1H NMR (300 MHz, CDCl3): δ 8.14 (d, 2H), 7.81 (s, 1H), 7.57-7.39 (m, 4H), 6.55 (d, 1H), 4.70 (br s, 1H), 3.72-3.55 (m, 1H), 3.35 (s, 3H), 3.24 (d, 2H), 2.22-2.11 (m, 2H), 1.95-1.85 (m, 2H), 1.76-1.50 (m, 3H), 1.33-1.07 (m, 4H).
Reaction SMILES: Br[CH2:2][C@@H:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH2:6][CH2:5][CH2:4]1.[C-:24]#[N:25].[K+]>CS(C)=O>[C:24]([CH2:2][C@@H:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[CH2:6][CH2:5][CH2:4]1)#[N:25]
Reactant: Cc1ccc(S(=O)(=O)N2CCC[C@H](CBr)c3ccccc32)cc1
Reactant: [C-]#N
Agent: [K+]
Solvent: CS(C)=O
Product: Cc1ccc(S(=O)(=O)N2CCC[C@H](CC#N)c3ccccc32)cc1
Temperature: 47.5 °C
Reaction time: 3 h
Yield: 83.7 %

Procedure:
A mixture of (5S)-5-bromomethyl-1-(p-toluenesulfonyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.83 g), potassium cyanide (0.27 g) and dimethyl sulfoxide (9 ml) is heated with stirring at 45-50° C. for three hours. To the reaction solution is added ice, and the mixture is extracted with ethyl acetate--diethyl ether. The extract is dried over sodium sulfate, and evaporated under reduced pressure to remove the solvent. The resulting residue is purified by silica gel column chromatography (solvent; n-hexane: ethyl acetate=6:1), and recrystallized from ethyl acetate--n-hexane to give (5R)-5-cyanomethyl-1-(p-toluenesulfonyl)-2,3,4,5-tetrahydro-1H-benzazepine (0.60 g).
Reaction SMILES: [Br:1][C:2]1[S:3][CH:4]=[C:5]([CH:7]=[O:8])[N:6]=1.[C:9]([Mg]Br)#[CH:10]>CCCCCC.C(OCC)(=O)C>[Br:1][C:2]1[S:3][CH:4]=[C:5]([CH:7]([C:9]#[CH:10])[OH:8])[N:6]=1
Reactant: C#C[Mg]Br
Reactant: O=Cc1csc(Br)n1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: C#CC(O)c1csc(Br)n1

Procedure:
Using the procedure of Example 1, 2-bromo-4-thiazole carboxaldehyde and ethynyl magnesium bromide were reacted to obtain the desired product with a Rf=0.17 [hexane-ethyl acetate (7-3)].
Reaction SMILES: Cl.[C:2]1([CH:8]=[CH:9][C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[OH:19]>>[O:11]1[C:3]2[C:2](=[CH:7][CH:6]=[CH:5][CH:4]=2)[C:8](=[O:19])[CH2:9][CH:10]1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CO
Reactant: O=C(C=Cc1ccccc1)c1ccccc1
Agent: Cl
Product: O=C1CC(c2ccccc2)Oc2ccccc21
Reaction time: 30 h

Procedure:
General procedure C for deprotection of the MOM group from chalcones to synthesize 7b, 7d, 7f. Concd HCl (0.25 mL/MOM group) was added to a solution of chalcone (1 mmol) in methanol (10 mL) at room temperature and the reaction mixture was stirred for 24-36 h until disappearance of starting material. The solvent was evaporated under reduced pressure and the residue was column chromatographed eluting with 25% ethyl acetate in hexanes to afford flavanone in high yield.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][CH2:15][OH:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:17][S:18](Cl)(=[O:20])=[O:19].C(N(CC)CC)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:14][CH2:15][O:16][S:18]([CH3:17])(=[O:20])=[O:19])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCCC[C@H]1CCO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCCC[C@H]1CCOS(C)(=O)=O

Procedure:
To a solution of (S)-2-(2-hydroxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester (0.300 g, 1.30 mmol) in dichloromethane (5 mL) was added methane sulfonylchloride 0.304 mL, 3.9 mmol) and triethylamine (0.547 mL, 3.9 mmol) at rt for 1-16 h. The reaction mixture was diluted with dichloromethane and washed with NaHCO3 (10%, W/V), followed by water. The dichloromethane layer was dried (Na2SO4), filtered and the solvent was evaporated to dryness. The product was sufficiently pure for the next step and was used without any further purification. LC-MS [M+Na] 329.9
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH2:8][O:9][CH3:10])[CH:7]=1.B([C:14]1[CH:19]=[CH:18][C:17]([C:20]([CH3:25])([CH3:24])[C:21]([OH:23])=[O:22])=[CH:16][CH:15]=1)(O)O.C([O-])([O-])=O.[K+].[K+]>COCCOC.O.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>[CH3:10][O:9][CH2:8][C:6]1[CH:7]=[C:2]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([CH3:25])([CH3:24])[C:21]([OH:23])=[O:22])=[CH:16][CH:15]=2)[CH:3]=[N:4][CH:5]=1
Reactant: COCc1cncc(Br)c1
Reactant: CC(C)(C(=O)O)c1ccc(B(O)O)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: [K+]
Solvent: COCCOC
Solvent: O
Product: COCc1cncc(-c2ccc(C(C)(C)C(=O)O)cc2)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 87.8 %

Procedure:
3-bromo-5-(methoxymethyl)pyridine (example 32b) (4.8 g, 23.56 mmol), 2-(4-boronophenyl)-2-methylpropanoic acid (example 21b) (5.4 g, 25.92 mmol) and K2CO3 (6.5 g, 47.12 mmol) were mixed in DME (60 mL) and 15 ml of water (15 mL). The mixture was degassed for 30 minutes and Pd(PPh3)4 (0.55 g, 0.47 mmol) was added. The reaction mixture was heated to reflux for 16 hr then cooled to room temperature, and evaporated under reduced pressure. The residue was diluted with aqueous NaOH (0.5 N, 60 mL) and stirred for 30 min., and the solution extracted with ether (20 mL×3). The aqueous phase was cooled to 0° C., acidified with 2 N HCl to PH=5˜6, then extracted with EtOAc. The organic phase was washed successively with water and brine, dried over MgSO4, filtered and evaporated. The residue was triturated with hexane, filtered and evaporated to give 5.9 g of 2-(4-(5-(methoxymethyl)pyridine-3-yl)phenyl)-2-methylpropanoic acid as a light brown solid in 88% yield. 1H NMR (400 MHz, CDCl3): δ 1.66 (s, 6H), 3.44 (s, 3H), 4.54 (s, 2H), 7.54-7.56 (d, 4H), 7.92 (s, 1H), 8.56 (s, 1H), 8.76 (s, 1H). MS (M+H, 286).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:20]([OH:22])=[O:21])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N1CCOCC1)C.[N+:31]([C:34]1[CH:39]=[CH:38][C:37](OC(ON=C(C#N)C(OCC)=O)=O)=[CH:36][CH:35]=1)([O-:33])=[O:32]>C(Cl)Cl>[N+:31]([C:34]1[CH:39]=[CH:38][C:37]([O:21][C:20](=[O:22])[C@H:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[NH:11][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])=[CH:36][CH:35]=1)([O-:33])=[O:32]
Reactant: CCOC(=O)C(C#N)=NOC(=O)Oc1ccc([N+](=O)[O-])cc1
Reactant: O=C(N[C@@H](Cc1ccccc1)C(=O)O)OCc1ccccc1
Agent: CCN1CCOCC1
Solvent: ClCCl
Product: O=C(N[C@@H](Cc1ccccc1)C(=O)Oc1ccc([N+](=O)[O-])cc1)OCc1ccccc1
Yield: 47.5 %

Procedure:
to a solution of N-benzyloxycarbonyl-L-phenylalanine (1.5 g) and 4-ethylmorpholine (0.63 ml) in dry methylene chloride (20 ml), ethyl 2-p-nitrophenyloxycarbonyloxyimino-2-cyanoacetate (1.55 g) is added at room temperature while stirring. The resulting mixture is stirred for 3 hours and extracted with ethyl acetate. The extract is washed with water, dried and concentrated. The residue is triturated with ethanol, and the obtained powder is collected by filtration and dried to give N-benzyloxycarbonyl-L-phenylalanine p-nitrophenyl ester (1.0 g). M.P. 124° - 126°C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:13][CH:12](OS(C)(=O)=O)[CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:19]([NH2:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O>[CH2:19]([NH:26][CH:12]1[CH2:13][N:10]([C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH2:11]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CS(=O)(=O)OC1CN(c2ccc([N+](=O)[O-])cc2)C1
Reactant: NCc1ccccc1
Solvent: O
Product: O=[N+]([O-])c1ccc(N2CC(NCc3ccccc3)C2)cc1
Temperature: 100 °C
Reaction time: 48 h
Yield: 81.2 %

Procedure:
Methanesulfonic acid 1-(4-nitro-phenyl)-azetidin-3-yl ester (which was obtained in Example 397) (14.32 g, 52.6 mmol) was added to neat benzyl amine (56 mL, 526 mmol) and stirred at 100° C. for 2 days. Water (200 mL) was added and the resultant precipitate was collected and partitioned between ethyl acetate and saturated aqueous NaHCO3. The aqueous layer was washed with ethyl acetate (2×50 mL). The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated. The solid was washed with diethyl ether and dried to give 12.1 g of the desired product as an orange solid; 1H NMR (300 MHz, CDCl3) δ1.66 (brs, 1H), 3.72(m, 2H), 3.82 (s, 2H, 3.89(m, 1H), 4.19(t, 2H, J=7.77 Hz), 6.29(d, 2H, J=9.12 Hz), 7.34(m, 5H), 8.07(d, 2H, J=9.18 Hz); MS (ES) m/z: 283.8 (MH+); Anal. Calcd. for C16H17N3O2: C, 67.83; H, 6.05; N, 14.83. Found: C, 67.59; H, 6.04; N, 14.79.
Reaction SMILES: [CH:1]1([C:6]#[CH:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.O1CCCC1.C([Li])CCC.CCCCCC.Cl[C:25]([O:27][CH3:28])=[O:26]>>[CH:1]1([C:6]#[C:7][C:25]([O:27][CH3:28])=[O:26])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C#CC1CCCC1
Reactant: COC(=O)Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COC(=O)C#CC1CCCC1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 95.7 %

Procedure:
To a stirred solution of cyclopentylacetylene (7, 17.49 mL, 150.0 mmol) in anhydrous tetrahydrofuran (THF, 200 mL, 2466 mmol) at −78° C. was added 2.50 M of n-butyllithium in hexane (66.0 mL, 165 mmol, 1.1 equiv). The resulting milky suspension was stirred at −78° C. for 30 min. Methyl chloroformate (17.6 mL, 225 mmol, 1.5 equiv) was then added. The reaction mixture became a clear solution. The cooling bath was then removed, and the reaction mixture was allowed to warm to room temperature and stirred at room temperature for 1 h. The reaction mixture became a suspension again. When TLC (5% EtOAc/hexane, KMnO4 stain) showed the reaction was deemed complete, the reaction mixture was quenched with saturated aqueous NH4Cl solution (150 mL) and extracted with diethyl ether (Et2O, 2×200 mL). The combined organic layers were washed with saturated aqueous NaCl solution, dried over magnesium sulfate (MgSO4), filtered and concentrated under the reduced pressure. The residue was distilled under vacuum (99-101° C./16 mbar) to afford methyl 3-cyclopentylpropiolate (18, 21.856 g, 22.83 g theoretical, 96% yield) as a colorless oil. For 18: 1H NMR (CDCl3, 400 MHz) δ ppm 3.74 (s, 3H), 2.73 (m, 1H), 1.95 (m, 2H), 1.72 (m, 4H), 1.57 (m, 2H).
Reaction SMILES: [CH3:1][C:2]([C:4]1[C:9]([NH2:10])=[CH:8][C:7]([O:11][CH3:12])=[C:6]([O:13][CH3:14])[CH:5]=1)=[O:3].[C:15]([OH:19])(=[O:18])[CH:16]=[CH2:17]>C(O)(=O)C>[C:2]([C:4]1[CH:5]=[C:6]([O:13][CH3:14])[C:7]([O:11][CH3:12])=[CH:8][C:9]=1[NH:10][CH2:17][CH2:16][C:15]([OH:19])=[O:18])(=[O:3])[CH3:1]
Reactant: C=CC(=O)O
Reactant: COc1cc(N)c(C(C)=O)cc1OC
Solvent: CC(=O)O
Product: COc1cc(NCCC(=O)O)c(C(C)=O)cc1OC
Temperature: 90 °C
Yield: 84.2 %

Procedure:
A mixture of 2-amino-4,5-dimethoxyacetophenone (910 g, 4.66 mol), acrylic acid (730 ml., 10.67 mol), and acetic acid (2100 ml) was heated at 90° C. for 2 hours. Following treatment with Darco and hot filtration, the product was precipitated by the addition of water (2475 ml) over a 1 hour period. The reaction mixture was cooled and the product was filtered and washed with cold distilled water (4×90 ml) and cold methanol (1×600 ml). Drying under vacuum at 60° C. gave 1049 g (84%) of the product as a yellow powder, mp 149.5°-151.5° C. NMR (CDCl3) δ 2.50 (s, 3H, ArCOCH3), 2.73 (t, 2H, CH2 --CO2H), 3.57 (t, 2H, N--CH2), 3.82 (s, 3H, CH3OAr), 3.93 (s, 3H, CH3OAr), 6.18 (s, 1H, ArH), 7.13 (s, 1H, ArH), 10.05 (broad s, 2H, NH, COOH).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][Si:5]([O:10][CH3:11])([O:8][CH3:9])[O:6][CH3:7].[N-:12]=[N+:13]=[N-:14].[Na+]>C(#N)C>[N:12]([CH2:2][CH2:3][CH2:4][Si:5]([O:10][CH3:11])([O:8][CH3:9])[O:6][CH3:7])=[N+:13]=[N-:14]
Reactant: [N-]=[N+]=[N-]
Reactant: CO[Si](CCCCl)(OC)OC
Agent: [Na+]
Solvent: CC#N
Product: CO[Si](CCCN=[N+]=[N-])(OC)OC

Procedure:
1.0 mole of 3-chloropropyltrimethoxysilane and 1.1 moles of sodium azide were heated in the presence of 3 mole percent of the catalyst described in Example 1 (a) in 500 ml of acetonitrile for eight hours with stirring and under reflux. After separation of the salt the subsequent distillation under reduced pressure gave the 3-azidopropyltrimethoxysilane now in a yield of 95 weight percent.
Reaction SMILES: Br[C:2]1[C:10]2[O:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=[C:4]([O:19][CH3:20])[CH:3]=1.[C:21]([Cu])#[N:22]>CN(C=O)C.C(OCC)(=O)C>[CH3:20][O:19][C:4]1[CH:3]=[C:2]([C:21]#[N:22])[C:10]2[O:9][C:8]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[N:7][C:6]=2[CH:5]=1
Reactant: N#C[Cu]
Reactant: COc1ccc(-c2nc3cc(OC)cc(Br)c3o2)cc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COc1ccc(-c2nc3cc(OC)cc(C#N)c3o2)cc1
Temperature: 150 °C
Yield: 50.7 %

Procedure:
To 7-bromo-5-methoxy-2-(4-methoxy-phenyl)-benzooxazole (200 mg) in DMF (5 mL) was added CuCN (80 mg). The mixture was placed in an oil bath and heated to 150° C. for 3 h. The mixture was cooled to room temperature and diluted with ethyl acetate and washed with 1N HCl, brine (3×), dried (Na2SO4), and concentrated. Flash chromatography on silica gel eluting with 20% ethyl acetate-hexane afforded 85 mg (50%) of the title compound as a solid. MS: 281 (MH+), HPLC tR: 2.71 min.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([NH:23][C:24]([CH:26]2[CH2:29][CH2:28][CH2:27]2)=[O:25])[C:16]2[C:21]([Cl:22])=[N:20][CH:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:30]1(C(O)=O)CCC1>>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:15]([NH:23][C:24]([CH:26]2[CH2:27][CH2:28][CH2:29][CH2:30]2)=[O:25])[C:16]2[C:21]([Cl:22])=[N:20][CH:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)C1CCC1
Reactant: O=C(NC(c1cccc(OCc2ccccc2)c1)c1nccnc1Cl)C1CCC1
Product: O=C(NC(c1cccc(OCc2ccccc2)c1)c1nccnc1Cl)C1CCCC1

Procedure:
Cyclopentanecarboxylic acid [(3-benzyloxy-phenyl)-(3-chloro-pyrazin-2-yl)-methyl]-amide (compound of Formula II where R1=cyclopentyl and Q1=Ph-(3-OBn)) was prepared according to the procedures described for the synthesis of cyclobutanecarboxylic acid [(3-benzyloxy-phenyl)-(3-chloro-pyrazin-2-yl)-methyl]amide (compound of Formula III where R1=cyclobutyl and Q1=Ph-(3-OBn)) above except for the substitution of cyclopentane carboxylic acid for cyclobutanecarboxylic acid; MS (ES) 422.2 (M+1), 424.2 (M+3).
Reaction SMILES: [CH3:1][N:2]([CH3:20])[C:3]([C:5]1[N:14]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10](Cl)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].C(OC([N:28]1[CH2:33][CH2:32][CH:31]([NH:34][C:35]([C:37]2[CH:38]=[N:39][C:40]([NH2:43])=[CH:41][CH:42]=2)=[O:36])[CH2:30][CH2:29]1)=O)(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH3:1][N:2]([CH3:20])[C:3]([C:5]1[N:14]([CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[C:8]2[N:9]=[C:10]([NH:43][C:40]3[CH:41]=[CH:42][C:37]([C:35](=[O:36])[NH:34][CH:31]4[CH2:32][CH2:33][NH:28][CH2:29][CH2:30]4)=[CH:38][N:39]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4]
Reactant: CC(C)(C)OC(=O)N1CCC(NC(=O)c2ccc(N)nc2)CC1
Reactant: CN(C)C(=O)c1cc2cnc(Cl)nc2n1C1CCCC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CN(C)C(=O)c1cc2cnc(Nc3ccc(C(=O)NC4CCNCC4)cn3)nc2n1C1CCCC1
Yield: 40.2 %

Procedure:
Following Buchwald Method B, 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (25 mg, 0.85 mmol) and 4-[(6-amino-pyridine-3-carbonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester (27 mg, 0.094 mmol), followed by deprotection using 0.6 mL of TBAF in 2 mL of THF to give 7-cyclopentyl-2-[5-(piperidin-4-ylcarbamoyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (18 mg, 72%). MS (ESI) m/z 424.2 (M+H)+
Reaction SMILES: [S:1]1[CH2:6][CH2:5][CH2:4][S:3][CH:2]1[C@H:7]1[CH:11]=[CH:10][CH2:9][C@H:8]1[C:12]([OH:14])=[O:13].[N+](=[CH2:17])=[N-]>CO>[CH3:17][O:13][C:12]([C@H:8]1[C@@H:7]([CH:2]2[S:3][CH2:4][CH2:5][CH2:6][S:1]2)[CH:11]=[CH:10][CH2:9]1)=[O:14]
Reactant: O=C(O)[C@@H]1CC=C[C@@H]1C1SCCCS1
Reactant: C=[N+]=[N-]
Solvent: CO
Product: COC(=O)[C@@H]1CC=C[C@@H]1C1SCCCS1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
214 mg (0.93 mmole) of cis-3-(1,3-dithian-2-yl)-4-cyclopentene-2-carboxylic acid (as prepared in example 4) are dissolved in 3 ml. of dried methanol. To the cooled mixture (0° C), there is added an ethereal solution of diazomethane up to persistente yellow colour. The solution is stirred for 3 hours at room temperature, the solvent is evaporated under reduced pressure and the oily residue is purified by column chromatography (eluant C6H6 /CH3CO2C2H5 : 80/20) to yield cis-methyl-3-(1,3-dithian-2-yl)-4-cyclopentene-2-carboxylate.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:10][C@H:11]([CH:13]2[CH2:15][CH2:14]2)[CH3:12])=[O:9])=[N:6][CH:7]=1.Cl.Cl.C[Si](C)(C)CCOC[N:24]1[C:28]2[N:29]=[CH:30][N:31]=[C:32]([C:33]3[CH:34]=[N:35][N:36]([C:38]4([CH2:42][C:43]#[N:44])[CH2:41][NH:40][CH2:39]4)[CH:37]=3)[C:27]=2[CH:26]=[CH:25]1>>[C:43]([CH2:42][C:38]1([N:36]2[CH:37]=[C:33]([C:32]3[C:27]4[CH:26]=[CH:25][NH:24][C:28]=4[N:29]=[CH:30][N:31]=3)[CH:34]=[N:35]2)[CH2:41][N:40]([C:2]2[CH:3]=[CH:4][C:5]([C:8]([NH:10][C@H:11]([CH:13]3[CH2:15][CH2:14]3)[CH3:12])=[O:9])=[N:6][CH:7]=2)[CH2:39]1)#[N:44]
Reactant: C[Si](C)(C)CCOCn1ccc2c(-c3cnn(C4(CC#N)CNC4)c3)ncnc21
Reactant: C[C@H](NC(=O)c1ccc(Br)cn1)C1CC1
Agent: Cl
Product: C[C@H](NC(=O)c1ccc(N2CC(CC#N)(n3cc(-c4ncnc5[nH]ccc45)cn3)C2)cn1)C1CC1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 3, Step 2-3 starting from 5-bromo-N-[(1S)-1-cyclopropylethyl]pyridine-2-carboxamide (Example 2, Step 1) and {3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile dihydrochloride. LCMS (M+H)+: m/z=468.2. 1H NMR (400 MHz, DMSO-d6): δ 12.60 (s, 1H), 9.14 (s, 1H), 8.90 (s, 1H), 8.60 (s, 1H), 8.26 (d, J=8.0 Hz, 1H), 7.97 (d, J=3.0 Hz, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.84 (m, 1H), 7.28 (m, 1H), 7.12 (dd, J=8.0, 3.0 Hz, 1H), 4.68 (d, J=8.0 Hz, 2H), 4.43 (d, J=8.0 Hz, 2H), 3.80 (s, 2H), 3.39 (m, 1H), 1.12 (t, J=7.0 Hz, 3H), 1.05 (m, 1H), 0.45 (m, 1H), 0.38 (m, 1H), 0.22 (m, 1H).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]3[O:15][CH2:16][CH2:17][O:18][C:11]=3[CH:10]=2)[C:5]([F:19])=[CH:4][N:3]=1.[F:20][C:21]([F:30])([F:29])[C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=1)[NH2:25]>>[CH2:17]1[CH2:16][O:15][C:12]2[CH:13]=[CH:14][C:9]([NH:8][C:6]3[C:5]([F:19])=[CH:4][N:3]=[C:2]([NH:25][C:24]4[CH:26]=[CH:27][CH:28]=[C:22]([C:21]([F:20])([F:29])[F:30])[CH:23]=4)[N:7]=3)=[CH:10][C:11]=2[O:18]1
Reactant: Fc1cnc(Cl)nc1Nc1ccc2c(c1)OCCO2
Reactant: Nc1cccc(C(F)(F)F)c1
Product: Fc1cnc(Nc2cccc(C(F)(F)F)c2)nc1Nc1ccc2c(c1)OCCO2

Procedure:
In like manner to the preparation of N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidinediamine, the reaction of 2-chloro-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-4-pyrimidineamine with 3-trifluoromethylaniline gave N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-trifluoromethylphenyl)-2,4-pyrimidinediamine. LCMS: ret. time: 25.88 min.; purity: 89%; MS (m/e): 407 (MH+).