Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:24])[NH:10][N:11]=[CH:12][C:13]=2[C:14]2[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.Br[C:26]1[CH:31]=[CH:30][C:29]([F:32])=[C:28]([F:33])[CH:27]=1.N>O>[F:32][C:29]1[CH:30]=[C:31]([N:10]2[C:9](=[O:24])[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[C:13]([C:14]3[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][CH:15]=3)[CH:12]=[N:11]2)[CH:26]=[CH:27][C:28]=1[F:33]
Reactant: Fc1ccc(Br)cc1F
Reactant: CS(=O)(=O)c1ccc(-c2cn[nH]c(=O)c2-c2ccc(Cl)cc2)cc1
Agent: N
Solvent: O
Product: CS(=O)(=O)c1ccc(-c2cnn(-c3ccc(F)c(F)c3)c(=O)c2-c2ccc(Cl)cc2)cc1

Procedure:
The title compound was prepared according to Example 93, starting with 4-(4-chlorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone in place of 4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone and substituting 1-bromo-3,4-difluorobenzene in place of 4-bromothioanisole (yield: 310 mg, 65.7%). mp 187-188° C. 1H NMR (300 MHz, CDCl3) δ 3.09 (s, 3H), 7.18 (d, J=9 Hz, 2H), 7.29 (m, 3H), 7.41 (d, J=9 Hz, 2H), 7.52 (m, 1H), 7.65 (m, 1H), 7.92 (d, J=9 Hz, 2H), 8.01 (s, 1H). MS (DCI/NH3) m/z 473 (M+H)+, 490 (M+NH4)+. Anal. calc. for C23H15ClF2N2O3S.0.5 H2O: C, 57.38; H, 3.33; N, 5.82. Found: C, 57.44; H, 3.38; N, 5.52.
Reaction SMILES: [CH:1]1([CH2:4][NH:5][CH2:6][C:7]2[CH:8]=[C:9](C3C=C4C(=C(C(N)=O)C=3)NC=C4C3CCN(S(CC)(=O)=O)CC3)[CH:10]=[N:11][CH:12]=2)CC1.[CH3:36][C:37]1([CH3:52])[C:41]([CH3:43])([CH3:42])[O:40][B:39](C2C=C(C=O)C=NC=2)[O:38]1.C(N)C.C1COCC1.[BH3-]C#N.[Na+]>>[CH2:4]([NH:5][CH2:6][C:7]1[CH:12]=[N:11][CH:10]=[C:9]([B:39]2[O:40][C:41]([CH3:43])([CH3:42])[C:37]([CH3:52])([CH3:36])[O:38]2)[CH:8]=1)[CH3:1]
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cncc(CNCC5CC5)c4)cc23)CC1
Reactant: CC1(C)OB(c2cncc(C=O)c2)OC1(C)C
Agent: CCN
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: C1CCOC1
Product: CCNCc1cncc(B2OC(C)(C)C(C)(C)O2)c1

Procedure:
Following the general procedure of 5-(5-{[(cyclopropylmethyl)amino]methyl}-3-pyridinyl)-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide, 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinecarbaldehyde (30 mg, 0.129 mmol), a 2 M solution of ethylamine in THF (0.065 mL, 0.129 mmol), and NaCNBH3 (16 mg, 0.258 mmol) were reacted to give 19 mg of crude ethyl{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methyl}amine. The crude ethyl{[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methyl}amine was then reacted with 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (30 mg, 0.0723 mmol), potassium carbonate (60 mg, 0.434 mmol), and chloro-2-(dimethylaminomethyl)-ferrocen-1-yl-(dinorbornylphosphine)palladium(II) (4.4 mg, 0.00723 mmol) to give 12.3 mg of the title compound (36%).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=[N:2]1.[H-].[Na+].Cl[CH2:20][C:21]1[CH:22]=[CH:23][C:24]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)=[N:25][CH:26]=1.O>CN(C)C=O>[Cl:33][C:30]1[CH:29]=[CH:28][C:27]([C:24]2[CH:23]=[CH:22][C:21]([CH2:20][O:16][C:13]3[CH:12]=[CH:11][C:10]([CH2:9][CH2:8][CH2:7][CH2:6][N:1]4[CH:5]=[CH:4][N:3]=[N:2]4)=[CH:15][CH:14]=3)=[CH:26][N:25]=2)=[CH:32][CH:31]=1
Reactant: ClCc1ccc(-c2ccc(Cl)cc2)nc1
Reactant: Oc1ccc(CCCCn2ccnn2)cc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Clc1ccc(-c2ccc(COc3ccc(CCCCn4ccnn4)cc3)cn2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 68.8 %

Procedure:
A solution of 91 mg (0.42 mmol) 4-(4-[1,2,3]triazol-1-yl-butyl)phenol in 4.0 ml N,N-dimethylformamide was treated at 0° C. with 18 mg (0.44 mmol) of 60% sodium hydride and stirred at 0° C. for 30 min. Then 100 mg (0.42 mmol) 5-Chloromethyl-2-(4-chloro-phenyl)-pyridine (GB 1147068) were added and stirred continued over night. After addition of 8 ml water, the precipitate was isolated, washed thoroughly with water, methanol/water 1:1 and diisopropylether. The residue was dried at 40° C. to give 121 mg (69%) of the title compound as light brown powder.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([OH:8])[C:5]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]#[N:18])=[CH:12][CH:11]=2)=[C:4]([CH3:19])[N:3]=1.[C:20]1([CH3:32])[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([CH3:27])[C:21]=1[S:28](Cl)(=[O:30])=[O:29]>CN(C1C=CN=CC=1)C>[CH3:32][C:20]1[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([CH3:27])[C:21]=1[S:28]([O:8][C:6]1[C:5]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]#[N:18])=[CH:12][CH:11]=2)=[C:4]([CH3:19])[N:3]=[C:2]([NH2:1])[N:7]=1)(=[O:29])=[O:30]
Reactant: Cc1nc(N)nc(O)c1Cc1ccc(CC#N)cc1
Reactant: Cc1cc(C)c(S(=O)(=O)Cl)c(C)c1
Agent: CN(C)c1ccncc1
Product: Cc1cc(C)c(S(=O)(=O)Oc2nc(N)nc(C)c2Cc2ccc(CC#N)cc2)c(C)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A mixture of the product from step (iii) (3.4 g), 2-mesitylenesulfonyl chloride (3.51 g), TEA (5.59 ml) and DMAP (82 mg) was stirred at rt for 18 h. The mixture was partitioned between DCM/water, the organics separated, washed with aq. NaHCO3 soln, water, dried and evaporated under reduced pressure. The residue was triturated with ether/ethylacetate and filtered to afford the subtitle compound, 5.08 g.
Reaction SMILES: C[O:2][C:3](=[O:31])[CH:4]=[C:5]([C:7]1[CH:8]=[CH:9][C:10]2[O:14][N:13]=[C:12]([C:15]3[CH:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[CH:18]=[C:17]([CH:24]([CH3:26])[CH3:25])[C:16]=3[O:27][CH2:28][CH3:29])[C:11]=2[CH:30]=1)[CH3:6].Cl>CO.[OH-].[Na+]>[CH2:28]([O:27][C:16]1[C:17]([CH:24]([CH3:26])[CH3:25])=[CH:18][C:19]([CH:21]([CH3:22])[CH3:23])=[CH:20][C:15]=1[C:12]1[C:11]2[CH:30]=[C:7]([C:5]([CH3:6])=[CH:4][C:3]([OH:31])=[O:2])[CH:8]=[CH:9][C:10]=2[O:14][N:13]=1)[CH3:29]
Reactant: CCOc1c(-c2noc3ccc(C(C)=CC(=O)OC)cc23)cc(C(C)C)cc1C(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCOc1c(-c2noc3ccc(C(C)=CC(=O)O)cc23)cc(C(C)C)cc1C(C)C

Procedure:
A solution of 3-[3-(2-ethoxy-3,5-diisopropyl-phenyl)-benzo[d]isoxazol-5-yl]-but-2-enoic acid methyl ester (99.6 mg, 0.24 mmol) in 2 mL of methanol and 2 ml of 1N NaOH solution was heated this mixture to 60° C. for 3 h, then cooled and brought to pH 2 with 1N HCl. The reaction mixture was extracted with ethyl acetate (2×10 mL), and the organic layers were dried over MgSO4 and evaporated to a residue. The residue was purified by silica gel chromatography (50% ethyl acetate in hexanes) to give a clear oil, which solidified upon standing to a waxy solid (12.1 mg, 13%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][C:12](=[O:29])[CH:13]([C:20]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[S:9][CH:10]=1)=[O:5])C.S(=O)(=O)(O)O>CO>[CH3:1][O:3][C:4]([C:6]1[N:7]=[C:8]([NH:11][C:12](=[O:29])[CH:13]([C:20]2[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[CH:24][CH:25]=2)[CH2:14][CH:15]2[CH2:16][CH2:17][CH2:18][CH2:19]2)[S:9][CH:10]=1)=[O:5]
Reactant: CCOC(=O)c1csc(NC(=O)C(CC2CCCC2)c2ccc([N+](=O)[O-])cc2)n1
Agent: O=S(=O)(O)O
Solvent: CO
Product: COC(=O)c1csc(NC(=O)C(CC2CCCC2)c2ccc([N+](=O)[O-])cc2)n1
Yield: 55.3 %

Procedure:
A solution of 2-[3-cyclopentyl-2-(4-nitro-phenyl)-propionylamino]-thiazole-4-carboxylic acid ethyl ester (prepared as in Example 39(B)(b), 135 mg, 0.32 mmol) in methanol (10 mL) was treated with a catalytic amount of sulfuric acid. The reaction mixture was heated under reflux for 68 h. The reaction was concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded 2-[3-cyclopentyl-2-(4-nitro-phenyl)-propionylamino]-thiazole-4-carboxylic acid methyl ester (71.4 mg, 54.8%) as a pale yellow solid: EI-HRMS m/e calcd for C19H21N3O5S (M+) 403.1201, found 403.1188.
Reaction SMILES: [P:1](Cl)([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1)([S:3][CH2:4][CH2:5][CH2:6][CH3:7])=[S:2].[OH:20][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[C:29]=1[C:28](=[O:30])[CH2:27][CH2:26]2.C(N(CC)CC)C>C1(C)C=CC=CC=1>[P:1]([O:20][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[C:29]=1[C:28](=[O:30])[CH2:27][CH2:26]2)([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1)([S:3][CH2:4][CH2:5][CH2:6][CH3:7])=[S:2]
Reactant: CCCCSP(=S)(Cl)Oc1ccc(C(F)(F)F)cc1
Reactant: O=C1CCc2cccc(O)c21
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Product: CCCCSP(=S)(Oc1ccc(C(F)(F)F)cc1)Oc1cccc2c1C(=O)CC2
Temperature: 0 °C
Reaction time: 8 h

Procedure:
S-n-Butyl O-(4-trifluoromethylphenyl) chlorodithiophosphate (0.015 mole) dissolved in dry toluene (80) is charged into a glass reaction vessel equipped with a stirrer, thermometer and gas inlet tube. The solution is cooled to about 0° C. and a solution of 7-hydroxyindan-1-one (0.015 mole) and triethylamine (0.0175 mole) in toluene (20 ml) is slowly added with stirring. After the addition is completed the reaction mixture is allowed to warm to room temperature and stirring is continued for a period of about 8 hours. After this time the reaction mixture is filtered and the filtrate is washed with water. The washed solution is then dried and is stripped of solvent leaving a residue. This residue is chromatographed through a 200 ml clay column using ethyl acetate and hexane mixtures as the eluant. Ten separate fractions each containing increasing percentages of ethyl acetate are collected and analyzed by IR for the product. The appropriate fractions are then combined stripped of solvent and subjected to vacuum to yield the desired product S-n-butyl O-(4-trifluoromethylphenyl) O-indan-1-on-7-yl dithiophosphate.
Reaction SMILES: [C:1]1([CH:7]=[CH:8][C:9]2[CH:13]=[C:12]([CH2:14][CH2:15][CH:16]=O)[O:11][N:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18]1([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[C:18]1([N:24]2[CH2:29][CH2:28][N:27]([CH2:16][CH2:15][CH2:14][C:12]3[O:11][N:10]=[C:9]([CH:8]=[CH:7][C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH:13]=3)[CH2:26][CH2:25]2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: O=CCCc1cc(C=Cc2ccccc2)no1
Reactant: c1ccc(N2CCNCC2)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: C(=Cc1cc(CCCN2CCN(c3ccccc3)CC2)on1)c1ccccc1
Yield: 48.2 %

Procedure:
About 2 min after dissolving 3-[3-(2-phenylvinyl)isoxazol-5-yl]propanal (20 mg, 0.09 mmol) and 1-phenylpiperazine (13.4, 0.09 mmol) in 2 mL of dry methylene chloride, were added NaBH(OAc)3 (56 mg, 0.26 mmol) and molecular sieves (5 beads). The reaction mixture was reacted for 22 hr and followed the same processes as in Example 1 to obtain 16.2 mg (49.3%) of the target compound.
Reaction SMILES: [C:1]1([C:7]([OH:12])([CH2:9][CH:10]=C)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:13]=[O+][O-].[BH4-].[Na+]>C(Cl)Cl>[C:1]1([C:7]([OH:12])([CH3:8])[CH2:9][CH2:10][OH:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CCC(C)(O)c1ccccc1
Reactant: O=[O+][O-]
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Product: CC(O)(CCO)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 2-phenylpent-4-en-2-ol (74 g, 0.457 mol) in dry CH2Cl2 (1 L) was treated with ozone at −78° C. until the mixture turned blue. The system was then flushed with oxygen to remove excess ozone. NaBH4 (42.8 g, 1.143 mol) was added to the mixture in portions at −20° C. The mixture was stirred overnight at rt. The mixture was quenched with water and the layers were separated. The aqueous layer was extracted with CH2Cl2 (2×). The organic layers were combined, washed with brine, dried over anhydrous Na2SO4 and concentrated to give 3-phenylbutane-1,3-diol (67.8 g), which was used for the next step without purification.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[S:16][C:17]3[C:22](Cl)=[N:21][C:20]([S:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[N:19][C:18]=3[N:32]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:33][C@@H:34]([CH2:39][OH:40])[CH2:35][CH:36]([CH3:38])[CH3:37]>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[S:16][C:17]3[C:22]([NH:33][C@@H:34]([CH2:39][OH:40])[CH2:35][CH:36]([CH3:38])[CH3:37])=[N:21][C:20]([S:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[N:19][C:18]=3[N:32]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(Nc2nc3nc(SCc4ccccc4)nc(Cl)c3s2)CC1
Reactant: CC(C)C[C@@H](N)CO
Solvent: C1CCOC1
Product: CC(C)C[C@H](CO)Nc1nc(SCc2ccccc2)nc2nc(NC3CCN(C(=O)OC(C)(C)C)CC3)sc12
Temperature: 100 °C
Yield: 76.8 %

Procedure:
The product from step (a) (50 mg, 0.1 mmol) and D-leucinol (60 mg, 0.5 mmol) were dissolved in anhydrous tetrahydrofuran (3 mL). The solution was heated in a capped reaction tube at 100° C. for 7 days. The crude product was flash chromatographed on silica (gradient eluent—ammonia:ethyl acetate:chloroform, 1:9:90 to 1:49:50). The product was dried in vacuo at room temperature resulting in 44 mg (76% yield) of the title compound as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=2)=[CH:10][CH:9]=1)=[O:6].[O:38]1[CH2:42][CH2:41][CH2:40][CH:39]1[CH2:43][NH2:44]>>[F:1][C:2]1[CH:3]=[C:4]([CH:29]=[C:30]([N:32]2[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]2)[CH:31]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][C:19]2[CH:24]=[CH:23][N:22]=[C:21]([NH:44][CH2:43][CH:39]3[CH2:40][CH2:41][CH2:42][O:38]3)[N:20]=2)=[CH:10][CH:9]=1)=[O:6]
Reactant: NCC1CCCO1
Reactant: CS(=O)(=O)c1nccc(Oc2ccc(NC(=O)c3cc(F)cc(N4CCCCC4)c3)c3ccccc23)n1
Product: O=C(Nc1ccc(Oc2ccnc(NCC3CCCO3)n2)c2ccccc12)c1cc(F)cc(N2CCCCC2)c1

Procedure:
Compound is prepared from 3-fluoro-N-[4-(2-methanesulfonyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-5-piperidin-1-yl-benzamide and C-(tetrahydrofuran-2-yl)-methylamine according to conditions described in general procedure C. 1H NMR (400 MHz, DMSO-d6) δ 1.40-1.65 (m, 10 H), 3.00-3.85 (m, 9 H), 6.327 (bs, 1 H), 6.96 (d, 1 H), 7.15 (d, 1 H), 7.38 (d, J=8.0 Hz, 1 H), 7.43 (s, 1 H), 7.54-7.60 (m, 3 H), 7.78-7.82 (m, 1 H), 7.96 (d, 1 H), 8.20 (s, 1 H), 10.41 (s, 1 H).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]([O:10]C)=[O:9])=[CH:4][N:3]=1.[CH:12]([OH:15])([CH3:14])[CH3:13]>>[CH:12]([O:15][C:2]1[N:3]=[CH:4][C:5]([C:8]([OH:10])=[O:9])=[CH:6][N:7]=1)([CH3:14])[CH3:13]
Reactant: CC(C)O
Reactant: COC(=O)c1cnc(Cl)nc1
Product: CC(C)Oc1ncc(C(=O)O)cn1
Yield: 14 %

Procedure:
The title compound was synthesized as described for Intermediate example I-81 in 14% yield starting from methyl 2-chloropyrimidine-5-carboxylate and isopropanol.
Reaction SMILES: Cl.O[CH2:3][C:4]1[N:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.CCN(C(C)C)C(C)C.[O:20](C(OC(C)(C)C)=O)[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=O>CN(C=O)C>[C:24]([O:23][C:21]([N:9]1[CH2:8][CH:7]([OH:10])[CH2:6][CH2:5][CH:4]1[CH3:3])=[O:20])([CH3:27])([CH3:26])[CH3:25]
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Reactant: OCc1ccc(O)cn1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC1CCC(O)CN1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 18 h
Yield: 17.5 %

Procedure:
1.50 g (9.28 mmol) of 6-Hydroxymethyl-pyridin-3-ol hydrochlorid was hydrogenated under the conditions described in intermediate 63B. The crude product was dissolved in 5 ml DMF, 5.60 ml (32.00 mmol) of Hunig's base and 3.56 g (16.00 mmol) of BOC2O were added and the yellow solution was stirred 18 h at RT. Evaporation, extraction (AcOEt/water/brine) and chromatography (silica gel, AcOEt/MeOH) gave 0.35 g (15%) (rac)-5-hydroxy-2-methyl-piperidine-1-carboxylic acid tert-butyl ester; MS: 216.4 (MH+)
Reaction SMILES: CCCCC.[H-].[Na+].[Br:8][C:9]1[N:14]=[C:13]2[CH2:15][C:16](=[O:18])[NH:17][C:12]2=[CH:11][CH:10]=1.Cl[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[CH:22][N+:21]=1[O-:33]>CN(C=O)C>[Br:8][C:9]1[N:14]=[C:13]2[C:15]([C:20]3[CH:25]=[CH:24][C:23]([CH2:26][N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[CH:22][N+:21]=3[O-:33])=[C:16]([OH:18])[NH:17][C:12]2=[CH:11][CH:10]=1
Reactant: O=C1Cc2nc(Br)ccc2N1
Reactant: [O-][n+]1cc(CN2CCOCC2)ccc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCCCC
Product: [O-][n+]1cc(CN2CCOCC2)ccc1-c1c(O)[nH]c2ccc(Br)nc12
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a suspension of previously pentane-washed sodium hydride on mineral oil (75 mg, 1.88 mmol) in DMF (2 mL) was added slowly 5-bromo-1H-pyrrolo[3,2-b]pyridin-2(3H)-one (300 mg, 1.41 mmol). The resulting green solution was further stirred for 10 minutes at RT. Then a solution of 215 mg (0.939 mmol) of 2-chloro-5-(morpholinomethyl)-pyridine 1-oxide prepared like in example 2.2 in DMF was added and the resulting mixture was heated to 130° C. and stirred for further 30 min. The reaction was cooled to RT and all volatiles were removed under reduced pressure. The residue was taken up in 2 M HCl (60 mL) and washed with ethyl acetate. The aqueous layer was carefully saturated with solid NaHCO3 and extracted with ethyl acetate. The combined organic phases were dried over MgSO4, filtered, and evaporated yielding the titled compound as a red oil.
Reaction SMILES: I[CH2:2][C:3]([N:6]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[N:7]1)([CH3:5])[CH3:4].[N-:14]=[N+:15]=[N-:16].[Na+].O>CN(C)C=O>[N:14]([CH2:2][C:3]([N:6]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[N:7]1)([CH3:5])[CH3:4])=[N+:15]=[N-:16]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(CI)n1cc([N+](=O)[O-])cn1
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(CN=[N+]=[N-])n1cc([N+](=O)[O-])cn1
Temperature: 140 °C
Reaction time: 8 h
Yield: 100.3 %

Procedure:
To a solution of 1-(1-iodo-2-methylpropan-2-yl)-4-nitro-1H-pyrazole (14 g) obtained in Step B of Example 115 in N,N-dimethylformamide (100 mL) was added sodium azide (4.8 g), and the mixture was stirred overnight at 140° C. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (10 g).
Reaction SMILES: [CH:1]([Si:3]([Cl:6])([Cl:5])[Cl:4])=[CH2:2].[Cl:7][SiH:8]([Cl:10])[Cl:9]>>[Cl:4][Si:3]([Cl:6])([Cl:5])[CH2:1][CH2:2][Si:8]([Cl:10])([Cl:9])[Cl:7]
Reactant: C=C[Si](Cl)(Cl)Cl
Reactant: Cl[SiH](Cl)Cl
Product: Cl[Si](Cl)(Cl)CC[Si](Cl)(Cl)Cl
Yield: 98 %

Procedure:
As in Example 1, 53.3 grams (0.33 mol) of vinyltrichlorosilane was reacted with 46.1 grams (0.34 mol) of trichlorosilane to obtain 96.0 grams (yield 98%) of 1,2-bis(trichlorosilyl)ethane.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:18]([O:20][CH3:21])=[O:19])=[C:11]([CH2:13][O:14]COC)[N:12]=2)=[CH:4][CH:3]=1.Cl>CO.Cl.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]([C:18]([O:20][CH3:21])=[O:19])=[C:11]([CH2:13][OH:14])[N:12]=2)=[CH:6][CH:7]=1
Reactant: COCOCc1nc(-c2ccc(Cl)cc2)oc1C(=O)OC
Agent: Cl
Solvent: O
Solvent: CO
Product: COC(=O)c1oc(-c2ccc(Cl)cc2)nc1CO
Temperature: 25 °C
Reaction time: 8 h

Procedure:
144 mg (0.52 mmol) of the compound from Example 43A are initially charged in 0.5 ml of methanol, and 0.13 ml of 4 N hydrochloric acid are added. 3 drops of conc. hydrochloric acid are then added. The reaction mixture is stirred at RT for 8 h. The mixture is then diluted with about 5 ml of water and extracted three times with in each case 10 ml of diethyl ether. The combined organic phases are dried over magnesium sulfate and the solvent is removed on a rotary evaporator. The product obtained is used without further purification in the subsequent reaction.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([N+:27]([O-])=O)[CH:21]=2)[CH2:11][CH2:10]1.[Cl-].[NH4+]>CCO.O.[Fe]>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[N:9]1[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([CH:21]=2)[NH2:27])[CH2:13][CH2:14]1
Reactant: Cc1ccc(OCCCCN2CCN(c3cccc(Cl)c3Cl)CC2)cc1[N+](=O)[O-]
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: Cc1ccc(OCCCCN2CCN(c3cccc(Cl)c3Cl)CC2)cc1N
Reaction time: 8 h
Yield: 89.6 %

Procedure:
A mixture of intermediate 62 (180 mg, 0.41 mmol), Fe (70 mg, 1.23 mmol) and ammonium chloride (25 mg, 0.41 mmol) was dissolved in EtOH and H2O, and the solution was heated to reflux and stirred overnight. The solution was filtered, diluted with water, and then extracted with DCM. The combined organic layers were washed with saturated aq NaHCO3, brine, dried over anhydrous Na2SO4, and concentrated in vacuo to give 5-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-methylaniline (intermediate 63) (150 mg, 90%) as a yellow solid. HPLC: 99%, RT 3.197 min. MS (ESI) m/z 407.9 [M+H]+.
Reaction SMILES: [NH:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@H:2]([C:6]([O:8]N1C(=O)CCC1=O)=O)[CH:3]([CH3:5])[CH3:4].[NH2:23][C@H:24]([C:28]([OH:30])=[O:29])[CH:25]([CH3:27])[CH3:26].CCN(CC)CC>CN(C=O)C>[NH:1]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[C@H:2]([C:6]([NH:23][C@H:24]([C:28]([OH:30])=[O:29])[CH:25]([CH3:27])[CH3:26])=[O:8])[CH:3]([CH3:4])[CH3:5]
Reactant: CC(C)[C@H](N)C(=O)O
Reactant: CC(C)[C@H](NC(=O)OC(C)(C)C)C(=O)ON1C(=O)CCC1=O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)[C@H](NC(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)C)C(=O)O

Procedure:
Boc-Val-OSu (12.6 g, 40 mmol) and H-Val-OH (4.68 g, 40 mmol) were condensed in DMF (250 ml) for 96 hours in the presence of 2 ml Et3N. More Et3N was added when needed to maintain the reaction slightly basic. The remaining insoluble material was filtered off and the filtrate evaporated to dryness (45°). The residue was partitioned between ether and dilute H2SO4 (~1%) and the organic layer washed with water (3×), dried over Na2SO4 and evaporated to a foamy glass. The product was crystallized from ether and petroleum ether: Yield, 12.2 g (96.4 %); mp 155°-158°; [α]D25 = +1.10° (c 1, DMF.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5](F)=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[CH3:12][N:13]([CH3:19])[CH2:14][CH2:15][CH2:16][NH:17][CH3:18]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:17]([CH3:18])[CH2:16][CH2:15][CH2:14][N:13]([CH3:19])[CH3:12])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1
Reactant: CNCCCN(C)C
Reactant: O=[N+]([O-])c1cc(Br)ccc1F
Product: CN(C)CCCN(C)c1ccc(Br)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a round bottom flask at 0° C. was added 4-Bromo-1-fluoro-2-nitrobenzene (10 g, 45.46 mmol) and N,N,N′-Trimethyl-propane-1,3-diamine (6.99 ml, 47.73 mmol). The reaction was allowed to warm to RT and stirred for 16 h. The reaction was extracted into EtOAc, washed once with saturated aqueous NaHCO3, twice with water, and then dried over Mg2SO4. The organic layer was filtered and concentrated to yield the title compound as a bright orange solid.