Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH2:14]O)=[C:12]([CH:16]([CH3:18])[CH3:17])[N:11]=[C:10]([N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])[N:9]=2)=[CH:4][CH:3]=1.Cl[P:26]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[OH-:39].[K+].O>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[C:27]1([P:26]([CH2:14][C:13]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[N:9][C:10]([N:19]([CH3:24])[S:20]([CH3:23])(=[O:22])=[O:21])=[N:11][C:12]=2[CH:16]([CH3:18])[CH3:17])([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:39])[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: [OH-]
Reactant: ClP(c1ccccc1)c1ccccc1
Reactant: CC(C)c1nc(N(C)S(C)(=O)=O)nc(-c2ccc(F)cc2)c1CO
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O
Product: CC(C)c1nc(N(C)S(C)(=O)=O)nc(-c2ccc(F)cc2)c1CP(=O)(c1ccccc1)c1ccccc1
Temperature: 111 °C
Reaction time: 1 h

Procedure:
A suspension of 9.29 g (26.3 mmol) of [4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]methanol in 26 g of toluene was, with ice-bath cooling, admixed with 7.64 g (34.4 mmol) of chlorodiphenylphosphine. After rinsing with a little toluene, the mixture was heated at 111° C. for 2 h. After cooling to room temperature, 4.94 g of a 45 percent strength potassium hydroxide solution and 873 mg (2.71 mmol) of tetrabutylammonium bromide were added, and the mixture was stirred vigorously at 60° C. for 1 h. 100 ml of water was added to the warm reaction mixture. The mixture was briefly stirred at 60° C. and slowly cooled to 4° C., and the precipitated solid was filtered off. The product was washed with cold water (30 ml) and cold toluene (30 ml) and dried under reduced pressure at 40° C. 11.74 g (78.4 percent; content: 94.4 percent) of N-[5-(diphenylphosphinoylmethyl)-4-(4-fluorophenyl)-6-isopropylpyrimidin-2-yl]-N-methylmethanesulfonamide was isolated in the form of a colorless solid.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([NH:11][C@@H:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][C@@H:13]2[OH:21])=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2].N[C@@H:23]1C2C(=CC=CC=2)CC[C@H]1O>>[CH2:1]([C:3]1[C:4]([NH:11][C@@H:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:23][CH2:14][C@H:13]2[OH:21])=[N:5][C:6]([CH2:9][CH3:10])=[CH:7][N:8]=1)[CH3:2]
Reactant: N[C@@H]1c2ccccc2CC[C@H]1O
Reactant: CCc1cnc(CC)c(N[C@@H]2c3ccccc3C[C@@H]2O)n1
Product: CCc1cnc(CC)c(N[C@@H]2c3ccccc3CC[C@H]2O)n1

Procedure:
Following the procedure for the preparation of (1R,2S)-1-[(3,6-diethylpyrazin-2-yl)amino]-2,3-dihydro-1H-inden-2-ol but substituting (trans)-1-amino-1,2,3,4-tetrahydronaphthalen-2-ol and making non-critical variations provided the title compound as a oil: 1H NMR (CDCl3) δ 1.27-1.34, 2.01, 2.24, 2.64, 2.84, 2.93, 4.03, 4.76, 5.06, 5.17, 7.19-7.21, 7.25-7.27, 7.34-7.37, 7.66;
Reaction SMILES: [C:1]([C:4]1[C:5](=[O:24])[NH:6][C:7]2[C:12]([C:13]=1C)=[C:11]([N+:15]([O-:17])=[O:16])[C:10](OS(O)(=O)=O)=[CH:9][C:8]=2[Cl:23])(=[O:3])[CH3:2].[Cl:25][C:26]1[CH:33]=[CH:32][C:29]([CH2:30][NH2:31])=[CH:28][CH:27]=1>>[C:1]([C:4]1[C:5](=[O:24])[NH:6][C:7]2[C:12]([C:13]=1[NH:31][CH2:30][C:29]1[CH:32]=[CH:33][C:26]([Cl:25])=[CH:27][CH:28]=1)=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=[CH:9][C:8]=2[Cl:23])(=[O:3])[CH3:2]
Reactant: CC(=O)c1c(C)c2c([N+](=O)[O-])c(OS(=O)(=O)O)cc(Cl)c2[nH]c1=O
Reactant: NCc1ccc(Cl)cc1
Product: CC(=O)c1c(NCc2ccc(Cl)cc2)c2c([N+](=O)[O-])ccc(Cl)c2[nH]c1=O
Yield: 57.1 %

Procedure:
3-Acetyl-8-chloro-4-methylsulfoxy-5-nitro-2-quinolinone (3.28g, 0.01 mol ) and p-chlorobenzylamine (1.42g, 0.01 mol) were used, but the reaction was carried out as the above process of example 37 to obtain the desired product (2.32g, yield: 57%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([S:30][CH2:31][CH3:32])=[C:18]([CH:29]=2)[CH2:19][N:20]([CH3:28])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:12])=[CH:4][CH:3]=1.[C:33](OC(=O)N(CC1C=C(N)C=CC=1SC(C)C)C)(C)(C)C.BrC1C=CC(C(CC)C(O)=O)=CC=1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([S:30][CH:31]([CH3:33])[CH3:32])=[C:18]([CH:29]=2)[CH2:19][N:20]([CH3:28])[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:12])=[CH:6][CH:7]=1
Reactant: CC(C)Sc1ccc(N)cc1CN(C)C(=O)OC(C)(C)C
Reactant: CCSc1ccc(NC(=O)CCCc2ccc(Br)cc2)cc1CN(C)C(=O)OC(C)(C)C
Agent: CCC(C(=O)O)c1ccc(Br)cc1
Product: CC(C)Sc1ccc(NC(=O)CCCc2ccc(Br)cc2)cc1CN(C)C(=O)OC(C)(C)C
Yield: 89 %

Procedure:
Using a procedure analogous to that used for preparation of 17B, 16E (0.418 g, 1.35 mmol) was reacted with 4-bromophenylbutanoic acid (0.340 g, 1.40 mmol) to give 18A (0.642 g, 89%) as a white solid. MS (ESI) m/z 537.0 (M+H)+.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.Cl[CH2:26][C:27]([CH2:29][CH3:30])=[CH2:28]>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)([CH2:28][C:27]([CH2:29][CH3:30])=[CH2:26])[CH:10]=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C1=C(c2ccccc2)CCN(Cc2ccccc2)C1
Reactant: C=C(CC)CCl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C=C(CC)CC1(c2ccccc2)C=CN(Cc2ccccc2)CC1

Procedure:
A solution of 1-benzyl-4-phenyl-1,2,5,6-tetrahydropyridine in tetrahydrofuran containing n-butyl lithium is added to a solution of 3-chloro-2-ethylpropene in tetrahydrofuran. The reaction is carried out according to the procedure of Example 1 to give 1-benzyl-4-phenyl-4-(2-ethylallyl)-1,4,5,6-tetrahydropyridine. The later compound is reacted with phosphoric acid and formic acid to give, after treatment with sodium hydroxide, 2-benzyl-3,4-dehydro-5-phenyl-7-ethylmorphan. Catalytic hydrogenation of the latter compound provides 2-benzyl-5-phenyl-7-ethylmorphan.
Reaction SMILES: [Br:1][C:2]1[C:7]2[N:8]=[CH:9][NH:10][C:6]=2[CH:5]=[C:4]([NH:11][C:12]2[NH:13][CH2:14][CH2:15][N:16]=2)[CH:3]=1.[Br:17]Br.CO.CCOC(C)=O>CC(O)=O>[Br:17][C:5]1[C:6]2[NH:10][CH:9]=[N:8][C:7]=2[C:2]([Br:1])=[CH:3][C:4]=1[NH:11][C:12]1[NH:13][CH2:14][CH2:15][N:16]=1
Reactant: Brc1cc(NC2=NCCN2)cc2[nH]cnc12
Reactant: BrBr
Solvent: CO
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: Brc1cc(NC2=NCCN2)c(Br)c2[nH]cnc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 136.4 %

Procedure:
To a solution of 7-bromo-5-(2-imidazolin-2-ylamino)benzimidazole (0.6 g, 2.10 mmol) in 10 ml of AcOH was added Br2 (0.057 ml, 1.1 mmol) in a portion. The resulting reaction mixture was stirred for 1 h at 25° C. Concentration of reaction mixture in vacuo yields a brown oil which was subjected to column chromatography (30% NH_sat'd MeOH/EtOAc) to provides 0.28 g (1.5 mmol, 71%) of the desired product. The product obtained was recrystallized from MeOH to afford 0.22 g (56%) of the product as a light brown solid: mp320-321° C.; Anal. Calc. for C10H9N5Br2 requires C, 33.45; H, 2.53; N, 19.51. Found: C, 33.93; H, 4.05; N, 19.01.
Reaction SMILES: C(OC(COC(=O)C)C[NH:7][C:8]([C:10]1[C:15]([I:16])=[C:14](N2[C@H](CO)COC2=O)[C:13]([I:25])=[C:12]([C:26]([NH:28]CC(OC(=O)C)COC(=O)C)=[O:27])[C:11]=1[I:40])=[O:9])(=O)C.C[O-].[Na+]>CO.O>[I:40][C:11]1[C:12]([C:26]([NH2:28])=[O:27])=[C:13]([I:25])[CH:14]=[C:15]([I:16])[C:10]=1[C:8]([NH2:7])=[O:9]
Reactant: CC(=O)OCC(CNC(=O)c1c(I)c(C(=O)NCC(COC(C)=O)OC(C)=O)c(I)c(N2C(=O)OC[C@H]2CO)c1I)OC(C)=O
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: NC(=O)c1c(I)cc(I)c(C(N)=O)c1I
Temperature: 25 °C
Reaction time: 1 h
Yield: 115.8 %

Procedure:
To a solution of N,N'-Bis[2,3-bis(acetyloxy)propyl]-5-(4)-(R)-(hydroxymethyl)-2-oxo-3-oxazolidinyl]-2,4,6-triiodo-1,3-benzenedicarboxamide of Example 2b (0.410 g, 0.51 mmol) in anhydrous methanol (7 ml) was added a methanolic solution of sodium methoxide (1.18 ml, 1M solution) and the mixture was stirred at room temperature for 1 h. The methanol was then removed on the rotary evaporator and water (8 ml) was added to redissolve the white residue. Dowex-50 (H+) was added to this solution portionwise to bring the pH down to approximately 7.0. The Dowex-50 resin was filtered off, water was removed on the rotary evaporator, and the white solid dried in vacuo at 60° over P2O5. The solid thus obtained (0.350 g) was redissolved in water (0.5 ml), seeded with a tiny crystal of the racemate and left overnight. The crystallized product was filtered, washed with cold water and dried overnight over P2O5 to obtain N,N'-Bis[2,3-bis(acetyloxy)propyl]-5-(4)-(R)-(hydroxymethyl)-2-oxo-3-oxazolidinyl]-2,4,6-triiodo-1,3-benzenedicarboxamide as white crystalline needles (0.32 g, 84%).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[N:11]=[N:10][C:9]([NH2:12])=[N:8][CH:7]=1.CO.[Br:15]Br>O>[Br:15][C:5]1[S:1][C:2]([C:6]2[N:11]=[N:10][C:9]([NH2:12])=[N:8][CH:7]=2)=[N:3][CH:4]=1
Reactant: Nc1ncc(-c2nccs2)nn1
Reactant: BrBr
Solvent: CO
Solvent: O
Product: Nc1ncc(-c2ncc(Br)s2)nn1
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 36.5 %

Procedure:
To a vial was added 6-(thiazol-2-yl)-1,2,4-triazin-3-amine (600 mg, 3.4 mmol), methanol (1.2 mL), water (0.6 mL). The mixture was cooled to 0° C. and bromine (816 mg, 5.1 mmol) was added. The reaction was stirred for 45 min and then quenched with saturated sodium bicarbonate solution (20 mL) and extracted three times with ethyl acetate (50 mL). The organic layers were dried over Na2SO4, concentrated, and purified using silica gel chromatography to afford 320 mg of 6-(5-bromothiazol-2-yl)-1,2,4-triazin-3-amine as an off-white solid.
Reaction SMILES: [Cl-:1].[Cl-].[Cl-].[CH:4]1([Ti+3:9])[CH:8]=[CH:7][CH:6]=[CH:5]1.[OH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1.C(N(CC)CC)C>CCOCC>[Cl-:1].[Cl-:1].[CH:4]1([Ti+2:9][O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[CH:8]=[CH:7][CH:6]=[CH:5]1
Reactant: Oc1ccccn1
Reactant: [Ti+3]C1C=CC=C1
Agent: [Cl-]
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: C1=CC([Ti+2]Oc2ccccn2)C=C1
Reaction time: 8 h

Procedure:
To a solution of 0.002 moles of cyclopentadienyl titanium trichloride in 50 mL of ether a solution of 2-hydroxy pyridine (0.002 moles) and triethylamine (0.002 moles) in 50 mL of ether was added at 0° C. and stirred overnight. The product was recovered from the ether filtrate. The product has the formula: ##STR12##
Reaction SMILES: C(Cl)C=C.[S].[CH2:6]([CH:8]([CH2:11][CH3:12])[CH:9]=O)[CH3:7].CC(CC)C=O.[N:19]1[C:20](=[S:24])[N:21]=CC=1>>[CH3:9][CH:8]([C:11]1[CH:12]=[N:21][C:20](=[S:24])[N:19]=1)[CH2:6][CH3:7]
Reactant: CCC(C=O)CC
Reactant: S=C1N=CC=N1
Agent: CCC(C)C=O
Agent: [S]
Solvent: C=CCCl
Product: CCC(C)C1=NC(=S)N=C1
Yield: 61 %

Procedure:
Allyl chloride was used for protecting the sulfur before oxidation for all of these examples. Racemic 4-(2-butyl)imidazole-2-thione 7G was prepared from racemic 2-ethylbutanal by this approach. The synthesis was repeated with optically active 2-methylbutanal to show that an aldehyde with a chiral carbon adjacent to the carbonyl leads to an enantiomerically enriched imidazole-2-thione. The chiral aldehyde was obtained in 61% yield by oxidizing (S)-(−)-2-methyl-1-butanol with oxalyl chloride and DMSO at −50° C. The Strecker reaction followed by Dibal-H reduction gave desired diamine 18H in 21% yield for two steps. Treatment with 1,1′-thiocarbonyldiimidazole, protecting the sulfur with allyl chloride followed by Swern oxidation gave 21H in 56% yield for three steps. The desired imidazole-2-thione 7H was obtained in 40% yield by deprotecting 21H with p-toluenesulfinic acid in the presence of a catalytic amount of Pd(P Ph3)4. Hplc analysis showed an enantiomeric ratio of 98:2 indicating scant racemization through the several steps.
Reaction SMILES: [CH3:1][C:2]([OH:6])([CH3:5])[C:3]#[CH:4].Br[C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1/[C:10](=[CH:18]/[C:19]1[NH:20][CH:21]=[CH:22][C:23]=1[O:24][CH3:25])/[C:11](=[O:17])[NH:12]2>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.CN(C=O)C.CCN(CC)CC>[OH:6][C:2]([CH3:5])([CH3:1])[C:3]#[C:4][C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1/[C:10](=[CH:18]/[C:19]1[NH:20][CH:21]=[CH:22][C:23]=1[O:24][CH3:25])/[C:11](=[O:17])[NH:12]2
Reactant: C#CC(C)(C)O
Reactant: COc1cc[nH]c1/C=C1\C(=O)Nc2cccc(Br)c21
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1cc[nH]c1/C=C1\C(=O)Nc2cccc(C#CC(C)(C)O)c21

Procedure:
Using Method D above, 3-methyl-1-butyn-3-ol (150 mg, 1.78 mmol) (Aldrich) was coupled with (Z)-4-bromo-1,3-dihydro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one (101 mg, 0.32 mmol) (Starting Material 1 supra) using (Ph3P)2PdCl2 (30 mg) and Cul (16 mg) as catalyst in DMF (3 mL) and Et3N (3 mL) as solvent at 70° C. for 18 h to yield (Z)-1,3-dihydro-4-(3-hydroxy-3-methyl-1-butynyl)-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-2H-indol-2-one. (Yield 43 mg, 38%).
Reaction SMILES: C([NH:8][CH:9]1[CH2:14][CH2:13][S:12](=[O:16])(=[O:15])[CH2:11][CH2:10]1)C1C=CC=CC=1.[H][H]>[OH-].[OH-].[Pd+2].C(O)C>[O:15]=[S:12]1(=[O:16])[CH2:13][CH2:14][CH:9]([NH2:8])[CH2:10][CH2:11]1
Reactant: O=S1(=O)CCC(NCc2ccccc2)CC1
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: NC1CCS(=O)(=O)CC1

Procedure:
N-Benzyl-1,1-dioxotetrahydro-2H-thiopyran-4-amine (2.00 g) was added to ethanol (40 mL) in a pressure bottle. Palladium hydroxide on carbon (0.587 g,) was added and the solution was stirred under 30 psi of hydrogen at room temperature for 2 hours. The mixture was filtered through a nylon membrane and the solvent was removed under vacuum.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[H-].[Na+].[C:8](=[S:10])=[S:9].[CH2:11](Cl)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CS(C)=O.C(OCC)C.O>[N:1]1([C:8]([S:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[S:9])[CH:5]=[CH:4][CH:3]=[CH:2]1
Reactant: c1cc[nH]c1
Reactant: ClCc1ccccc1
Reactant: S=C=S
Agent: [H-]
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Solvent: CS(C)=O
Product: S=C(SCc1ccccc1)n1cccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 50 %

Procedure:
Pyrrole (1.34 g, 20 mmol) was added dropwise, with stirring, to a suspension of sodium hydride (0.48 g, 20 mmol) in dimethyl sulphoxide (20 mL). Once the addition has ended, the resultant brown suspension was stirred for a further 30 min at room temperature before adding carbon disulphide (1.52 g, 20 mmol). The solution was stirred for a further 30 min at room temperature, and finally the benzyl chloride (2.53 g, 20 mmol) was added. After 1 h, water (20 mL) was added to the reaction mixture, followed by diethyl ether (20 mL). The organic phase was separated off, and then the aqueous phase was extracted twice, each time with 20 mL of diethyl ether. The combined organic phases were dried, using magnesium sulphate, and filtered, and the solvent was distilled off. The crude product was separated chromatographically, using 5% strength ethyl acetate in petroleum ether. The pure product was isolated in the form of a yellow oil at 50% yield (2.34 g).
Reaction SMILES: [O:1]1[CH2:3][C@H:2]1[CH2:4][O:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH2:8][CH2:9][C:10](=[O:16])[NH:11]2.[CH:17]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:20]=[CH:19][C:18]=1[N:27]1[CH2:34][C@H:33]2[NH:35][CH2:36][C@@H:28]1[CH2:29][CH:30]=[CH:31][CH2:32]2.C(O)C.CCN(C(C)C)C(C)C>C(Cl)Cl>[OH:1][CH:2]([CH2:3][N:35]1[CH2:36][CH:28]2[N:27]([C:18]3[CH:19]=[CH:20][C:21]4[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH:17]=3)[CH2:34][CH:33]1[CH2:32][CH:31]=[CH:30][CH2:29]2)[CH2:4][O:5][C:6]1[CH:15]=[CH:14][CH:13]=[C:12]2[C:7]=1[CH2:8][CH2:9][C:10](=[O:16])[NH:11]2
Reactant: C1=CC[C@H]2CN[C@@H](C1)CN2c1ccc2ccccc2c1
Reactant: O=C1CCc2c(cccc2OC[C@@H]2CO2)N1
Agent: C1=C\C[C@H]2CN[C@@H](C/1)CN2c1ccc2ccccc2c1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: O=C1CCc2c(cccc2OCC(O)CN2CC3CC=CCC2CN3c2ccc3ccccc3c2)N1
Temperature: 95 °C

Procedure:
(S)-5-Oxiranylmethoxy-3,4-dihydro-1H-quinolin-2-one (25 mg, 0.114 mmol) and Z-(1S,6S)-7-naphthalen-2-yl-7,9-diaza-bicyclo[4.2.2]dec-3-ene (30 mg, 0.114 mmol) were placed in a μW tube with ethanol (2 ml), CH2Cl2 (2 mL), DIPEA (100 μL, 0.576 mmol) and heated to 95° C. for 900 sec. The solvent was evaporated from the reaction mixture and the residue was purified via flash chromatography (gradient 10% to 100% Ethyl acetate/heptane) to yield the title compound as a residue.
Reaction SMILES: C([O-])(=O)C.[CH2:5]([P+:7]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH3:6].O.O.[C:28]([OH:33])(=[O:32])[C:29]([OH:31])=[O:30].C(O)(=O)C(O)=O>CO>[C:28]([O-:33])(=[O:32])[C:29]([O-:31])=[O:30].[CH2:5]([P+:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:6].[CH2:5]([P+:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH3:6]
Reactant: O=C(O)C(=O)O
Agent: CC(=O)[O-]
Agent: CC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CO
Solvent: O
Product: O=C([O-])C(=O)[O-]

Procedure:
To a 2 gallon bottle was charged 1000 g (1.707 mol) of a 70% methanol solution of ethyltriphenylphosphonium acetate.acetic acid complex followed by the addition of 204.4 g (1.622 mol) oxalic acid dihydrate. The mixture was mixed until all of the oxalic acid had dissolved and then about 31.5 g of methanol was added to give a resultant solution of about 50 wt. % ethyltriphenylphosphonium oxalate.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[C:6]([CH:13]([CH3:15])[CH3:14])[C:5]=1[NH:16][S:17]([C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=1)(=[O:19])=[O:18])([CH3:3])[CH3:2].[OH-].[Na+]>C(O)C.C(OCC)(=O)C>[NH2:10][C:8]1[CH:9]=[C:4]([CH:1]([CH3:3])[CH3:2])[C:5]([NH:16][S:17]([C:20]2[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=2)(=[O:19])=[O:18])=[C:6]([CH:13]([CH3:15])[CH3:14])[CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)Nc2c(C(C)C)cc([N+](=O)[O-])cc2C(C)C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cc1ccc(S(=O)(=O)Nc2c(C(C)C)cc(N)cc2C(C)C)cc1
Temperature: 80 °C
Yield: 75.9 %

Procedure:
To a suspension of N-(2,6-diisopropyl-4-nitro-phenyl)-4-methyl-benzenesulfonamide (3.72 g) in ethanol (50 mL) was added stannous(II) chloride dihydrate (11.2 g) and the mixture was heated to 80° C. for 1.5 hour. It was then poured onto ice (300 mL), made strongly basic with solid sodium hydroxide (20 g) and diluted with ethyl acetate (100 mL). The suspension was filtered and extracted with ethyl acetate (3×100 mL). The combined organic phases were dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography to furnish 2.60 g (76%) of the title compound as an off-white solid. 1H NMR (500 MHz, CDCl3): 0.95 (d, 12H), 2.40 (s, 3H), 3.02 (m, 2H), 3.68 (b, 2H), 5.74 (s, 1H), 6.39 (s, 2H), 7.23 (d, 2H), 7.60 (d, 2H).
Reaction SMILES: [OH:1][C:2]1(CO)[CH2:7][O:6][C@H:5]([C:8]2[CH:13]=[C:12]([F:14])[C:11]([F:15])=[CH:10][C:9]=2[F:16])[C@@H:4]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:3]1.I([O-])(=O)(=O)=O.[Na+]>O1CCCC1.O>[O:1]=[C:2]1[CH2:7][O:6][C@H:5]([C:8]2[CH:13]=[C:12]([F:14])[C:11]([F:15])=[CH:10][C:9]=2[F:16])[C@@H:4]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:3]1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC(O)(CO)CO[C@@H]1c1cc(F)c(F)cc1F
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N[C@H]1CC(=O)CO[C@@H]1c1cc(F)c(F)cc1F
Reaction time: 3 h

Procedure:
To a solution of tert-butyl [(2R,3S)-5-hydroxy-5-(hydroxymethyl)-2-(2,4,5-trifluorophenyl)tetrahydro-2H-pyran-3-yl]carbamate (223 mg, 0.59 mmol) in tetrahydrofuran (4 mL) was added a solution of sodium periodate (143 mg, 0.67 mmol) in water (1.3 mL) and the mixture stirred for 3 hours. The mixture was concentrated and purified by flash chromatography (silica, gradient 5-20% ethyl acetate in chloroform) to yield tert-butyl [(2R,3S)-5-oxo-2-(2,4,5-trifluorophenyl)tetrahydro-2H-pyran-3-yl]carbamate as white solid.
Reaction SMILES: [OH:1][NH:2][C:3](=[NH:14])[C:4]1[CH:9]=[CH:8][C:7]([S:10](=[O:13])(=[O:12])[NH2:11])=[CH:6][CH:5]=1.[F:15][CH:16]([F:36])[C:17]1[N:22]=[C:21]([C:23](O)=O)[N:20]=[C:19]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=2)[CH:18]=1>>[F:36][CH:16]([F:15])[C:17]1[CH:18]=[C:19]([C:26]2[CH:27]=[CH:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=2)[N:20]=[C:21]([C:23]2[O:1][N:2]=[C:3]([C:4]3[CH:9]=[CH:8][C:7]([S:10]([NH2:11])(=[O:12])=[O:13])=[CH:6][CH:5]=3)[N:14]=2)[N:22]=1
Reactant: N=C(NO)c1ccc(S(N)(=O)=O)cc1
Reactant: O=C(O)c1nc(-c2ccc(C(F)(F)F)cc2)cc(C(F)F)n1
Product: NS(=O)(=O)c1ccc(-c2noc(-c3nc(-c4ccc(C(F)(F)F)cc4)cc(C(F)F)n3)n2)cc1

Procedure:
The title compound was prepared from N-hydroxy-4-sulfamoyl-benzamidine [CAS-No. 4476-10-2] (0.16 g, 0.75 mmol) and 6-difluoromethyl-4-(4-trifluoromethyl-phenyl)-pyrimidine-2-carboxylic acid (example D.3) (0.16 g, 0.5 mmol) according to the general procedure V. Obtained as a white solid (0.096 g, 39%). MS (ISP) 498.3 [(M+H)+]; mp 307° C.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][CH2:8][C:9]2=O)=[CH:4][CH:3]=1.[CH3:13][Mg]I>>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5](=[CH:4][CH:3]=1)[CH2:6][CH2:7][CH:8]=[C:9]2[CH3:13]
Reactant: C[Mg]I
Reactant: O=C1CCCc2ccc(Cl)cc21
Product: CC1=CCCc2ccc(Cl)cc21

Procedure:
Using general procedure A (Exp. 1.1), 7-chloro-3,4-dihydro-2H-naphthalen-1-one (Lit. 13) was reacted with MeMgI to give 6-chloro-4-methyl-1,2-dihydro-naphthalene as a yellow oil. MS: 178.0 ([M]+).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]#[N:21])=[C:7]([C:12]3[CH:13]=[N:14][CH:15]=[C:16]([CH:18]=O)[CH:17]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1.[CH3:22][S:23]([NH2:26])(=[O:25])=[O:24].C(O)(=O)C.C(N(CC)CC)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]#[N:21])=[C:7]([C:12]3[CH:17]=[C:16]([CH2:18][NH:26][S:23]([CH3:22])(=[O:25])=[O:24])[CH:15]=[N:14][CH:13]=3)[N:8]2[CH3:11])=[CH:4][CH:3]=1
Reactant: CS(N)(=O)=O
Reactant: Cn1c(-c2cncc(C=O)c2)c(C#N)c2ccc(Cl)cc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CC(=O)O
Solvent: ClCCCl
Product: Cn1c(-c2cncc(CNS(C)(=O)=O)c2)c(C#N)c2ccc(Cl)cc21
Reaction time: 8 h

Procedure:
6-Chloro-2-(5-formyl-pyridin-3-yl)-1-methyl-1H-indole-3-carbonitrile (Example 126, 50 mg, 0.169 mmol) and methanesulfonamide (24 mg, 0.254 mmol), acetic acid (20 mg, 0.338 mmol), triethylamine (34 mg, 0.338 mmol) in DCE (10 mL) are stirred for 30 min at ambient temperature before adding NaBH(OAc)3 (100 mg, 0.473 mmol). The reaction mixture is stirred overnight. NaHCO3 (1 mL) is added and the solvents are removed in vacuo. The residue is purified using a Sunfire C18 with a gradient of acetonitrile in 0.1% aqueous TFA and further purified with an Xbridge C18 using a gradient of acetonitrile in 0.1% NH4OH to give N-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-ylmethyl]-methanesulfonamide as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.97 (s, 3H), 3.78 (s, 3H), 4.36 (s, 2H), 7.37 (dd, J=8.6, 1.8 Hz, 1H), 7.73 (d, J=8.6 Hz, 1H), 7.75 (br. s., 1H), 7.97 (d, J=1.8 Hz, 1H), 8.10 (t, J=2.1 Hz, 1H), 8.78 (d, J=2.0 Hz, 1H), 8.81 (d, J=2.3 Hz, 1H). HRMS (ESI) m/z 375.0681 [(M+H)+ Calcd for C17H16ClN4O2S: 375.0682].
Reaction SMILES: [Br:1][C:2]1[CH:13]=[C:6]2[C:7](O[C:10](=O)[NH:11][C:5]2=[CH:4][CH:3]=1)=[O:8].C([O-])(=O)C.C(N)=[NH2+:19]>CC(O)C>[Br:1][C:2]1[CH:13]=[C:6]2[C:5](=[CH:4][CH:3]=1)[N:11]=[CH:10][NH:19][C:7]2=[O:8]
Reactant: NC=[NH2+]
Reactant: O=c1[nH]c2ccc(Br)cc2c(=O)o1
Agent: CC(=O)[O-]
Solvent: CC(C)O
Product: O=c1[nH]cnc2ccc(Br)cc12
Temperature: 25 °C

Procedure:
A solution of 5-bromoisatoic anhydride (5.0 g, 21 mmol) and formamidinium acetate (2.2 g, 21 mmol) in 60 mL of i-PrOH was heated at reflux for 10 hours. The reaction mixture was cooled to rt and the white solid was collected by filtration. The white solid was washed with small amount of i-PrOH and dried in air to give desired product 6-bromoquinazolin-4(3H)-one. MS (ESI, pos. ion) m/z: 224.9 (M+1).