Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[C:16]2[C:17]3=[C:18]4[C:13](=[CH:14][CH:15]=2)[CH:12]=[CH:11][CH:10]=[C:9]4[CH:8]=[CH:7][C:6]3=[CH:5][CH:4]=1.[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][C:20]=1[C:29](Cl)=[O:30].ClCCCl.[Cl-].[Al+3].[Cl-].[Cl-]>CO>[CH:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][C:20]=1[C:29]([C:4]1[CH:5]=[C:6]2[C:17]3=[C:18]4[C:13]([CH:12]=[CH:11][CH:10]=[C:9]4[CH:8]=[CH:7]2)=[CH:14][CH:15]=[C:16]3[C:3]=1[O:2][CH3:1])=[O:30]
Reactant: O=C(Cl)c1ccc2ccccc2c1
Reactant: COc1ccc2ccc3cccc4ccc1c2c34
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Solvent: CO
Product: COc1c(C(=O)c2ccc3ccccc3c2)cc2ccc3cccc4ccc1c2c34
Reaction time: 2 h

Procedure:
Methoxy pyrene (23.20 g, 0.1 mol), 2-naphthoyl chloride (56.8 g, 0.333 mol), and 1,2-dichloroethane (325 g) were put in a flask. Then, aluminum chloride (29.4 g, 0.12 mol) was slowly added to the solution at ambient temperature, and the mixture was agitated for 2 hours. When the reaction was terminated, a precipitate obtained by adding methanol thereto was filtered, obtaining 2-naphthoyl methoxy pyrene.
Reaction SMILES: [C:1]1([CH:13]2[CH2:17][CH2:16][C@H:15]([NH2:18])[CH2:14]2)[C:5]2=[C:6]3[CH:12]=[CH:11][NH:10][C:7]3=[N:8][CH:9]=[C:4]2[NH:3][N:2]=1.Cl[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][N:21]=1.CCN(C(C)C)C(C)C>CCO>[C:1]1([C@H:13]2[CH2:17][CH2:16][C@H:15]([NH:18][C:20]3[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][N:21]=3)[CH2:14]2)[C:5]2=[C:6]3[CH:12]=[CH:11][NH:10][C:7]3=[N:8][CH:9]=[C:4]2[NH:3][N:2]=1
Reactant: N#Cc1ccc(Cl)nc1
Reactant: N[C@H]1CCC(c2n[nH]c3cnc4[nH]ccc4c23)C1
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: N#Cc1ccc(N[C@H]2CC[C@H](c3n[nH]c4cnc5[nH]ccc5c34)C2)nc1
Temperature: 120 °C
Yield: 4.9 %

Procedure:
A mixture of (1S)-3-(3,6-Dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridin-1-yl)cyclopentanamine (0.20 g, 0.83 mmol, Preparation #30), 6-chloronicotinonitrile (0.12 g, 0.83 mmol), DIEA (0.22 mL, 1.2 mmol), and EtOH (3 mL) were heated for about 1 h at about 120° C. in a microwave (250 psi maximum pressure, 1 min ramp, 300 max watts). The reaction mixture was concentrated in vacuo and purified by RP-HPLC (Table 2, Method s) to give 6-((1S,3S)-3-(3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridin-1-yl)cyclopentylamino)nicotinonitrile (0.014 g, 5%): LC/MS (Table 2, Method a) Rt=1.75 min; m/z: 344 (M+H)+ and 6-((1S,3R)-3-(3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridin-1-yl)cyclopentylamino)nicotinonitrile (0.020 g, 7%): LC/MS (Table 2, Method a) Rt=1.81 min; m/z: 344 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:11](=[C:13]([C:17]([OH:19])=O)[CH:14]=[CH:15][CH:16]=3)[N:12]=2)=[CH:4][CH:3]=1.Cl.Cl.[NH2:22][CH:23]1[CH2:30][CH:29]2[N:31]([CH3:32])[CH:25]([CH2:26][CH2:27][CH2:28]2)[CH2:24]1>>[CH3:32][N:31]1[CH:25]2[CH2:26][CH2:27][CH2:28][CH:29]1[CH2:30][CH:23]([NH:22][C:17]([C:13]1[CH:14]=[CH:15][CH:16]=[C:10]3[O:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)=[N:12][C:11]=13)=[O:19])[CH2:24]2
Reactant: O=C(O)c1cccc2oc(-c3ccc(F)cc3)nc12
Reactant: CN1C2CCCC1CC(N)C2
Agent: Cl
Product: CN1C2CCCC1CC(NC(=O)c1cccc3oc(-c4ccc(F)cc4)nc13)C2
Yield: 60 %

Procedure:
N-(9-Methyl-9-azabicyclo[3.3.1]non-3-yl)-2-(4-fluorophenyl)benzoxazole-4-carboxamide was prepared from 2-(4-fluorophenyl)benzoxazole-4-carboxylic acid and 3-amino-9-methyl-9-azabicyclo[3.3.1]nonane dihydrochloride using the method outlined in Step C of Example 14. This compound was obtained in 60% yield as a white solid: mp 197-199° C.; 1H NMR (500 MHz, CDCl3) δ 8.95 (m, 1H), 8.26 (m, 2H), 8.21 (dd, J=7.8, 1.0 Hz, 1H), 7.69 (dd, J=8.1, 1.0 Hz, 1H), 7.46 (t, J=7.9 Hz, 1H), 7.29 (m, 1H), 4.60 (m, 1H), 3.11 (m, 2H), 2.66 (m, 2H), 2.54 (s, 3H), 2.15 (m, 1H), 2.04 (m, 2H), 1.59 (m, 2H), 1.51 (m, 2H), 1.17 (m, 2H); MS (ESI) m/z 394 [M+H]+
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([F:11])=[CH:5][C:4]=1[C:12]1[CH:20]=[C:19]2[C:15]([CH:16]=[N:17][N:18]2C2CCCCO2)=[CH:14][CH:13]=1)[CH3:2].Cl>CO>[CH2:1]([C:3]1[CH:8]=[C:7]([O:9][CH3:10])[C:6]([F:11])=[CH:5][C:4]=1[C:12]1[CH:20]=[C:19]2[C:15]([CH:16]=[N:17][NH:18]2)=[CH:14][CH:13]=1)[CH3:2]
Reactant: CCc1cc(OC)c(F)cc1-c1ccc2cnn(C3CCCCO3)c2c1
Agent: Cl
Solvent: CO
Product: CCc1cc(OC)c(F)cc1-c1ccc2cn[nH]c2c1
Temperature: 60 °C
Yield: 106.9 %

Procedure:
To a solution of 6-(2-ethyl-5-fluoro-4-methoxy-phenyl)-1-(tetrahydro-pyran-2-yl)-1H-indazole (Preparation 14, 1.8 g, 5.07 mmol) in methanol (100 mL) was added concentrated hydrochloric acid (12M) and the resulting solution was heated at 60° C. overnight, cooled to room temperature and concentrated in vacuo. The residue was redissolved in EtOAc (50 mL) and washed with saturated sodium hydrogen carbonate aqueous solution (50 mL). The organic layer was dried over MgSO4 and concentrated in vacuo to yield the title product (1.465 g) in 95% yield.
Reaction SMILES: [CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]([N:24]4[CH2:29][CH2:28][CH:27]([CH2:30][CH2:31][CH2:32][C:33]([OH:35])=O)[CH2:26][CH2:25]4)=[O:23])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4].Cl.CN.F[P-](F)(F)(F)(F)F.[N:46]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:50]2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22]([N:24]4[CH2:29][CH2:28][CH:27]([CH2:30][CH2:31][CH2:32][C:33](=[O:35])[NH:46][CH3:50])[CH2:26][CH2:25]4)=[O:23])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4]
Reactant: CNC(=O)n1ccc2cc(Oc3ccnc(NC(=O)N4CCC(CCCC(=O)O)CC4)c3)ccc21
Reactant: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: CN
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CNC(=O)CCCC1CCN(C(=O)Nc2cc(Oc3ccc4c(ccn4C(=O)NC)c3)ccn2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 17.4 %

Procedure:
4-(1-((4-(1-Methylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonyl)piperidin-4-yl)butyric acid (170 mg, 0.35 mmol) was dissolved in N,N-dimethylformamide (7.0 ml); methylamine hydrochloride (48 mg, 0.71 mmol), benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (314 mg, 0.71 mmol) and triethylamine (0.35 ml) were added thereto; and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia NH silica gel, hexane-ethyl acetate-methanol system). After a small amount of acetone and ethyl acetate were added to the obtained amorphous solid; this solution was diluted with diethyl ether; and the solid portion was filtered off, washed with diethyl ether, and dried under aeration to yield the title compound (30 mg, 0.061 mmol, 17%) as a colorless amorphous solid.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:28][CH2:27][C:10]2[C:11]3[C:12](O)([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:13]([F:19])([F:18])[CH2:14][C:15]=3[CH:16]=[CH:17][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2].N1C=CC=CC=1.S(Cl)([Cl:37])=O>>[CH2:1]([O:3][C:4]([N:6]1[CH2:28][CH2:27][C:10]2[C:11]3[C:12]([Cl:37])([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:13]([F:19])([F:18])[CH2:14][C:15]=3[CH:16]=[CH:17][C:9]=2[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: O=S(Cl)Cl
Reactant: CCOC(=O)N1CCc2ccc3c(c2CC1)C(O)(c1ccccc1)C(F)(F)C3
Solvent: c1ccncc1
Product: CCOC(=O)N1CCc2ccc3c(c2CC1)C(Cl)(c1ccccc1)C(F)(F)C3
Temperature: 70 °C

Procedure:
Into a 100 ml flask, the product from step (c) (5.78 g, 14.93 mmol) dissolved in thionyl chloride (50 ml) was added. Pyridine (120 μL, 1.49 mmol) was added and the reaction mixture heated to 70° C. for 1 hour. The reaction mixture was allowed to cool to room temperature and the volatiles were evaporated in vacuo. The residue was partitioned between saturated aqueous Na2CO3 and EtOAc. The aqueous layer was extracted with EtOAc (3×). The combined EtOAc extracts were washed with brine, dried over Na2SO4, and solvent evaporated in vacuo to give the sub-title compound as an orange semi-solid (5.9 g) that was used directly in the next step. MS: ESI (positive): 405 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([C:8]2[S:12][C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[C:10]([CH2:19][C:20](O)=[O:21])[CH:9]=2)=[O:7])=[CH:4][CH:3]=1.[OH:25][N:26]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1.ON.Cl>C(Cl)Cl>[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([C:6]([C:8]2[S:12][C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[C:10]([CH2:19][C:20]([NH:26][OH:25])=[O:21])[CH:9]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: On1nnc2ccccc21
Reactant: O=C(O)Cc1cc(C(=O)c2ccc(Cl)cc2)sc1-c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: NO
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: O=C(Cc1cc(C(=O)c2ccc(Cl)cc2)sc1-c1ccccc1)NO
Reaction time: 8 h
Yield: 20.2 %

Procedure:
To a stirred mixture of 30 mg (0.08 mmol) of 1, 11 mg (0.08 mmol) of N-hydroxybenzotriazole (HOBt), 21 mg (0.11 mmol) of 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (EDCI.HCl), and 28 mL (0.25 mmol) of 4-methylmorpholine in 5 mL dry CH2Cl2 was added 6 mg (0.08 mmol) of HONH2.HCl at room temperature. The resulting mixture was stirred overnight and washed with 5 mL of H2O. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc) to give 6 mg (20%) of 2 as a white viscous residue that solidified slowly at room temperature: 1H NMR (400 MHz, DMSO-d6) δ 10.69 (s, 1H), 8.90 (brs, 1H), 7.86 (d, J=8.6 Hz, 2H), 7.72 (s, 1H), 7.68-7.50 (m, 7H), 3.39 (s, 2H); 13C NMR (100 MHz, DMSO-d6) 185.9, 166.3, 148.8, 139.7, 138.6, 137.4, 136.0, 133.0, 132.3, 130.6, 129.2, 129.2, 129.1, 128.9; IR (KBr) cm−1 3305, 3223, 3060, 2921, 1746, 1631, 1436; LREIMS C19H14ClNO3S requires 371.04. Found: 371 ([M+], 9%), 355 (100%).
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[C:12](=[O:14])[CH3:13].[BH4-].[Na+]>CO>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[CH:12]([OH:14])[CH3:13]
Reactant: CC(=O)c1ccc2ccccc2c1Br
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(O)c1ccc2ccccc2c1Br
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a mixture of 1-(1-bromo-2-naphthyl)ethanone (0.488 g, 1.96 mmol) in methanol (10 mL) was added sodium tetrahydroborate (0.0741 g, 1.96 mmol). The reaction was stirred at room temperature for 30 minutes, quenched with water, extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated to dryness under reduced pressure. The residue was used directly in next step (467 mg, 94%). LCMS calculated for C12H10Br(M−OH)+: m/z=233.0; found: 233.2.
Reaction SMILES: [C:1]([O:5][C:6](=[O:45])[NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:44])[NH:16][C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:24]3[N:29]4[N:30]=[CH:31][CH:32]=[C:28]4[CH:27]=[C:26]([C:33]4[CH:42]=[CH:41][C:40]5[C:35](=[CH:36][CH:37]=[C:38]([OH:43])[CH:39]=5)[CH:34]=4)[N:25]=3)=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:49][CH2:50][O:51][CH3:52]>CN(C=O)C>[C:1]([O:5][C:6](=[O:45])[NH:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:15](=[O:44])[NH:16][C:17]2[CH:22]=[CH:21][C:20]([NH:23][C:24]3[N:29]4[N:30]=[CH:31][CH:32]=[C:28]4[CH:27]=[C:26]([C:33]4[CH:42]=[CH:41][C:40]5[C:35](=[CH:36][CH:37]=[C:38]([O:43][CH2:49][CH2:50][O:51][CH3:52])[CH:39]=5)[CH:34]=4)[N:25]=3)=[CH:19][CH:18]=2)=[CH:13][CH:14]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NCc1ccc(C(=O)Nc2ccc(Nc3nc(-c4ccc5cc(O)ccc5c4)cc4ccnn34)cc2)cc1
Reactant: COCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCCOc1ccc2cc(-c3cc4ccnn4c(Nc4ccc(NC(=O)c5ccc(CNC(=O)OC(C)(C)C)cc5)cc4)n3)ccc2c1
Reaction time: 8 h
Yield: 52 %

Procedure:
To a solution of (4-{4-[5-(6-hydroxy-naphthalen-2-yl)-pyrazolo[1,5-c]pyrimidin-7-ylamino]-phenylcarbamoyl}-benzyl)-carbamic acid tert-butyl ester (compound A3)(120 mg) in DMF (3 ml) are added NaH (8 mg) and 2-bromoethylmethylether (0.019 ml). The mixture is stirred overnight and after extraction the crude product is purified by silica gel flash chromatography. A nearly colorless solid (68 mg) in 52% yield is obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:13][NH:12][CH2:11][CH:10]2[N:14]([CH3:25])[C:15](=[O:24])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH:26]1([CH2:29][N:30]2[CH2:35][CH2:34][CH:33]([C:36](O)=[O:37])[CH2:32][CH2:31]2)[CH2:28][CH2:27]1>>[CH:26]1([CH2:29][N:30]2[CH2:31][CH2:32][CH:33]([C:36]([N:12]3[CH2:13][CH:9]([C:4]4[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=4)[CH:10]([N:14]([CH3:25])[C:15](=[O:24])[CH2:16][C:17]4[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=4)[CH2:11]3)=[O:37])[CH2:34][CH2:35]2)[CH2:27][CH2:28]1
Reactant: O=C(O)C1CCN(CC2CC2)CC1
Reactant: CN(C(=O)Cc1ccc(F)cc1)C1CNCC1c1ccc(Cl)c(Cl)c1
Product: CN(C(=O)Cc1ccc(F)cc1)C1CN(C(=O)C2CCN(CC3CC3)CC2)CC1c1ccc(Cl)c(Cl)c1

Procedure:
In analogy to the procedure described for the synthesis of example 87 (step c), the title compound N-[(3RS,4RS)-1-(1-cyclopropylmethyl-piperidine-4-carbonyl)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-2-(4-fluoro-phenyl)-N-methyl-acetamide was prepared from N-[(3RS,4SR)-4-(3,4-dichloro-phenyl)-pyrrolidin-3-yl]-2-(4-fluoro-phenyl)-N-methyl-acetamide using 1-cyclopropylmethyl-piperidine-4-carboxylic acid instead of 1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid and was obtained as a colorless oil. MS m/e: 546.3 [M]+.
Reaction SMILES: Cl[CH2:2][C:3]([O:5][C@@H:6]1[C@@H:25]([O:26][CH2:27][CH3:28])[CH2:24][C@@:23]2([CH3:29])[C@@H:8]([CH2:9][CH2:10][C@@H:11]3[C@@H:22]2[C:21](=[O:30])[CH2:20][C@@:19]2([CH3:31])[C@H:12]3[CH2:13][CH2:14][C@@H:15]2[C:16](=[O:18])[CH3:17])[CH2:7]1)=[O:4].[I-:32].[Na+]>CC(C)=O>[CH2:27]([O:26][C@H:25]1[CH2:24][C@@:23]2([CH3:29])[C@@H:8]([CH2:9][CH2:10][C@@H:11]3[C@@H:22]2[C:21](=[O:30])[CH2:20][C@@:19]2([CH3:31])[C@H:12]3[CH2:13][CH2:14][C@@H:15]2[C:16](=[O:18])[CH3:17])[CH2:7][C@@H:6]1[O:5][C:3](=[O:4])[CH2:2][I:32])[CH3:28]
Reactant: CCO[C@H]1C[C@@]2(C)[C@@H](CC[C@H]3[C@@H]4CC[C@H](C(C)=O)[C@@]4(C)CC(=O)[C@@H]32)C[C@@H]1OC(=O)CCl
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: CCO[C@H]1C[C@@]2(C)[C@@H](CC[C@H]3[C@@H]4CC[C@H](C(C)=O)[C@@]4(C)CC(=O)[C@@H]32)C[C@@H]1OC(=O)CI
Yield: 85.1 %

Procedure:
3α-Chloroacetoxy-2β-ethoxy-5α-pregnane- 11,20-dione (450 mg) was dissolved in acetone (50 ml) and sodium iodide (460 mg) added to the solution. The mixture was refluxed for one-half hour, a white precipitate forming. The precipitate was filtered off and the filtrate evaporated to a yellow foam which ws partitioned between ether and water. The ethereal solution was dried over anhydrous sodium sulphate and evaporated to give 2β-ethoxy-3α-iodoacetoxy-5α-pregnane-11,20 -dione (460 mg) as a pale yellow foam.
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8](F)[C:7]([N+:11]([O-])=O)=[CH:6][C:3]=1[C:4]#[N:5].[NH4+:14].[OH-]>CCO.CCOC(C)=O.C(O)(=O)C.[Zn]>[NH2:14][C:8]1[C:7]([NH2:11])=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=1
Reactant: [NH4+]
Reactant: N#Cc1cc([N+](=O)[O-])c(F)cc1F
Agent: [OH-]
Agent: [Zn]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: N#Cc1cc(N)c(N)cc1F
Reaction time: 0.5 h

Procedure:
To a solution of 2,4-difluoro-5-nitrobenzonitrile (CAS #: 67152-20-9) (5.0 g, 27.2 mmol) in EtOH (100 mL) was added NH4OH (100 mL) slowly at room temperature. The mixture was stirred for 30 min, then concentrated under reduced pressure to about 100 mL. The yellow product was filtered and washed with water, and then dried. To a solution of the residue (3.96 g, 22 mmol) in EtOAc (150 mL) and acetic acid (25 mL) was added zinc (14.3 g, 219 mmol). The mixture was stirred at room temperature for 2 hour. The reaction mixture was diluted with EtOAc and filtered through a pad of Celite®. The Celite® pad was washed with EtOAc. The filtrate was concentrated, and the residue was dissolved in MeOH (50 mL) and NH4OH (100 mL). The mixture was then concentrated to around 100 mL and the mixture was left standing at room temperature overnight. The precipitate was filtered and washed with water, and then dried to give the title compound. MS (ESI+) m/z 152.1 (M+H).
Reaction SMILES: FC(F)(F)C(O[C:6]1[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[CH2:8][CH:7]=1)=O.C([Sn](CCCC)(CCCC)[C:21]1[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=1)CCC.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+]>CN1CCCC1=O.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].[Cu]I>[CH3:13][C:9]1([CH3:12])[CH2:10][CH2:11][C:6]([C:21]2[CH:26]=[CH:25][N:24]=[CH:23][CH:22]=2)=[CH:7][CH2:8]1
Reactant: CC1(C)CC=C(OC(=O)C(F)(F)F)CC1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccncc1
Agent: [Cu]I
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CN1CCCC1=O
Product: CC1(C)CC=C(c2ccncc2)CC1
Temperature: 90 °C
Reaction time: 25 h
Yield: 35.6 %

Procedure:
A solution of Example 12A (0.775 g. 3.0 mmol) and 4-tributylstannylpyridine (1.22 g, 3.3 mmol) in 1-methyl-2-pyrrolidinone (5 mL) was treated with Pd2(dba)3 (55 mg, 0.06 mmol), CuI (65 mg, 0.35 mmol), Ph3P (125 mg, 0.475 mmol) and K2CO3 (550 mg, 3.9 mmol), purged with argon, and stirred for 25 hours at 90° C. The reaction mixture was diluted with ethyl acetate (50 mL) and saturated aqueous potassium fluoride (10 mL), stirred 2 hours at room temperature, and filtered through a pad of diatomaceous earth (Celite®). The filtrate layers were separated and the organic phase was washed with water and brine, dried (Na2SO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 4:1 ethyl acetate and hexanes to provide 200 mg (36%) of the desired product. MS (ESI) m/e 188.1 (M+H)+.
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3[CH:10]=[CH:9][CH:8]([CH:4]2[CH:3]=[CH:2]1)[CH2:7]3.ClC(Cl)(Cl)C(Cl)(Cl)Cl.C1(C#C)C=CC=CC=1>C(Cl)Cl>[CH2:1]1[CH:5]2[C@@H:6]3[CH:10]=[CH:9][C@H:8]([CH:4]2[CH:3]=[CH:2]1)[CH2:7]3
Reactant: C1=CC2C3C=CC(C3)C2C1
Agent: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Solvent: C#Cc1ccccc1
Solvent: ClCCl
Product: C1=CC2C(C1)[C@@H]1C=C[C@H]2C1
Reaction time: 3 h

Procedure:
A 10.0 gram (75.6 mmol) amount of dicyclopentadiene was added to a 100 ml round-bottom flask. A 5.0 milligram (7.2 μmol) amount of RuClH(H2)(PCy3)2, ten equivalents of hexachloroethane, and ten equivalents of phenylacetylene were added via the addition of a 0.5 mls stock solution containing 2.5 mls of CH2Cl2, 25 mg RuClH(H2)(PCy3)2, 86 mg of hexachloroethane and 36 mg of phenylacetylene. The ring opening polymerization of dicyclopentadiene was observed slowly by a gradual thickening of the solution to a rubbery viscous material after three hours. After 24 hours, it had become a soft rubbery material.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]([CH:8]([CH3:16])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:4](=[O:17])[CH:3]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=1B(O)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>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:20]=1[C:2]1[CH:7]=[CH:6][N:5]([CH:8]([CH3:16])[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C:4](=[O:17])[CH:3]=1
Reactant: OB(O)c1cc(Cl)ccc1Cl
Reactant: CC(C(=O)OC(C)(C)C)n1ccc(Br)cc1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: CC(C(=O)OC(C)(C)C)n1ccc(-c2cc(Cl)ccc2Cl)cc1=O

Procedure:
2.5 g (8.0 mmol) of tert-butyl 2-(4-bromo-2-oxopyridin-1(2H)-yl)propanoate (racemate) and 1.76 g (9.2 mmol) of 2,5-dichlorophenylboronic acid in the presence of tetrakis(triphenylphosphine)palladium(0) were reacted according to General Method 2A. Yield: 2.3 g (77% of theory)
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH3:14])[CH:6]=1.[Na].BrCCCCC[Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24]>O1CCCC1.C(OCC)C.O>[CH3:1][O:2][C:3](=[O:15])[CH:4]([CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][O:2][Si:23]([C:26]([CH3:27])([CH3:28])[CH3:29])([CH3:24])[CH3:25])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[C:7]([O:13][CH3:14])[CH:6]=1
Reactant: COC(=O)Cc1ccc(OC)c(OC)c1
Reactant: CC(C)(C)[Si](C)(C)CCCCCBr
Agent: [Na]
Solvent: O
Solvent: CCOCC
Solvent: C1CCOC1
Product: COC(=O)C(CCCCCO[Si](C)(C)C(C)(C)C)c1ccc(OC)c(OC)c1
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 111.9 %

Procedure:
To a solution, -78° C. under argon, of 2.38 g of 3,4-dimethoxyphenyl acetic acid methyl ester in 30 ml of tetrahydrofuran is added 12.45 ml of 1.0M sodium hexamethylsidilazide. The solution is stirred at -78° C. for 5 minutes and then warmed to 0° C. for 1 hour. To this solution is added 3.5 g of (5-bromopentyl)(1,1-dimethylethyl)dimethyl silane. The reaction mixture is allowed to warm to room temperature and stirred for 12 hours. The mixture is diluted with diethyl ether and water, the layers are separated and the organic layer is washed with saturated sodium chloride, dried and concentrated in vacuo. The residue is purified by chromatography (silica gel: hexane/ethyl acetate,5/1) to give 2.6 g of the desired product as a clear oil.
Reaction SMILES: Cl.[OH:2][NH:3][C:4]([C@H:6]1[C:11]([CH3:13])([CH3:12])[S:10][CH2:9][CH2:8][N:7]1[S:14]([C:17]1[CH:37]=[CH:36][C:20]([O:21][CH2:22][C:23]#[C:24][CH2:25][CH2:26][CH2:27][NH:28]C(=O)OC(C)(C)C)=[CH:19][CH:18]=1)(=[O:16])=[O:15])=[O:5]>ClCCl.CO>[NH2:28][CH2:27][CH2:26][CH2:25][C:24]#[C:23][CH2:22][O:21][C:20]1[CH:36]=[CH:37][C:17]([S:14]([N:7]2[CH2:8][CH2:9][S:10][C:11]([CH3:12])([CH3:13])[C@@H:6]2[C:4]([NH:3][OH:2])=[O:5])(=[O:15])=[O:16])=[CH:18][CH:19]=1
Reactant: CC(C)(C)OC(=O)NCCCC#CCOc1ccc(S(=O)(=O)N2CCSC(C)(C)[C@@H]2C(=O)NO)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CO
Product: CC1(C)SCCN(S(=O)(=O)c2ccc(OCC#CCCCN)cc2)[C@H]1C(=O)NO
Yield: 108.5 %

Procedure:
Hydrogen chloride gas was bubbled into a solution of 0.104 g (0.192 mmol) of tert-butyl 6-[4({(3S)-3-[(hydroxyamino)carbonyl]-2,2-dimethylthiomorpholinyl}sulfonyl)phenoxy]-4-hexynylcarbamate in 6 mL of dichloromethane and 2 mL of methanol for 5 min, and the reaction was stoppered and let stand for 1h and then concentrated in vacuo. The residue was triturated with ether to provide 0.092 g (100%) of (3S)4({4 [(6-amino-2-hexynyl)oxy]phenyl}sulfonyl)N-hydroxy-2,2-dimethyl-3-thiomorpholine carboxamide as a cream solid. Electrospray Mass Spec: 442.1(N+H)+
Reaction SMILES: [C:1]([O:4][NH:5][C:6](=[NH:32])[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[O:14][C:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([C:25](=[NH:31])[NH:26]OC(=O)C)=[CH:21][CH:20]=3)=[CH:16][CH:17]=2)=[N:9][CH:8]=1)(=[O:3])[CH3:2].C(O)C>C(O)(=O)C.[Pd]>[C:1]([OH:4])(=[O:3])[CH3:2].[C:25]([C:22]1[CH:21]=[CH:20][C:19]([CH2:18][C:15]2[O:14][C:13]([C:10]3[CH:11]=[CH:12][C:7]([C:6]([NH2:32])=[NH:5])=[CH:8][N:9]=3)=[CH:17][CH:16]=2)=[CH:24][CH:23]=1)(=[NH:26])[NH2:31]
Reactant: CC(=O)ONC(=N)c1ccc(Cc2ccc(-c3ccc(C(=N)NOC(C)=O)cn3)o2)cc1
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Product: N=C(N)c1ccc(Cc2ccc(-c3ccc(C(=N)N)cn3)o2)cc1
Reaction time: 4 h
Yield: 60 %

Procedure:
To a solution of 37 (170 mg, mmol) in glacial acetic acid (8 mL), and ethanol (10 mL) was added 10% palladium on carbon (70 mg). The mixture was placed on Parr hydrogenation apparatus at 50 psi for 4 h at room temperature. The mixture was filtered off through HYFLO. The filtrate was evaporated under reduced pressure and the precipitate was collected and washed with ether to give 38 in 60% yield, mp 213–216° C.dec. 1H nmr (DMSO-d6); δ 1.78 (s, 6H), 6.43 (d, J=3.3 Hz, 1H), 7.23 (d, J=3.3 Hz, 1H), 7.43 (d, J=7.8 Hz, 2H), 7.49–7.73 (m, 3H), 8.17 (d, J=7.8 Hz, 1H), 8.89 (s, 1H). Calcd. for C18H17N5O-2AcOH-3H2O-0.35EtOH: C, 53.50; H, 6.54; N, 13.74. Found C, 53.57; H, 6.51; N, 13.37.