Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@@H:17]3[C@H:8]([C@H:9]4[C@:13]([CH2:15][CH2:16]3)([CH3:14])[CH:12]=[CH:11][CH2:10]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1.C12BC(CCC1)CCC2.[OH-:30].[Na+].OO>O1CCCC1.O>[CH3:1][O:2][C:3]1[CH:20]=[CH:19][C:18]2[C@@H:17]3[C@H:8]([C@H:9]4[C@:13]([CH2:15][CH2:16]3)([CH3:14])[CH2:12][C@H:11]([OH:30])[CH2:10]4)[CH2:7][CH2:6][C:5]=2[CH:4]=1
Reactant: [OH-]
Reactant: COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@@]2(C)C=CC[C@@H]12
Agent: B1C2CCCC1CCC2
Agent: OO
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc2c(c1)CC[C@@H]1[C@@H]2CC[C@@]2(C)C[C@H](O)C[C@@H]12
Temperature: 25 °C

Procedure:
0.81 g (3 mmol) of 3-methoxy-13α-estra-1,3,5(10),16-tetraene is dissolved under a cover gas in 10 ml of anhydrous tetrahydrofuran and mixed with 0.73 g of 9-bora-bicyclo[3.3.1]nonane. It is stirred at room temperature until the reaction is completed. Then, it is mixed with 15 ml of water. After gas generation is completed, 7.8 ml of 3 M sodium hydroxide solution is added. 7.8 ml of hydrogen peroxide solution (30%) is then slowly added in drops to the reaction mixture while being cooled. It is stirred for 1 hour at room temperature and extracted with ethyl acetate. The chromatography of the crude product on silica gel (eluant: cyclohexane/ethyl acetate 4+1) yields 604 mg of 3-methoxy-13α-estra-1,3,5(10)-trien-16α-ol in the form of a colorless oil.
Reaction SMILES: [C:1]([C:5]1[N:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([C:14]2[N:15]([C:33](Cl)=[O:34])[CH:16]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[CH:17]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)[N:18]=2)=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:36]([N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)(=[O:38])[CH3:37]>>[C:1]([C:5]1[N:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([C:14]2[N:15]([C:33]([N:42]3[CH2:43][CH2:44][N:39]([C:36](=[O:38])[CH3:37])[CH2:40][CH2:41]3)=[O:34])[C@H:16]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[C@H:17]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)[N:18]=2)=[CH:7][N:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOc1nc(C(C)(C)C)ncc1C1=NC(c2ccc(Cl)cc2)C(c2ccc(Cl)cc2)N1C(=O)Cl
Reactant: CC(=O)N1CCNCC1
Product: CCOc1nc(C(C)(C)C)ncc1C1=N[C@@H](c2ccc(Cl)cc2)[C@@H](c2ccc(Cl)cc2)N1C(=O)N1CCN(C(C)=O)CC1

Procedure:
cis-4-[2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (example 20) was reacted with 1-acetyl-piperazine (Aldrich) to give cis-1-{4-[2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-ethanone in an analogous manner as described in example 1. HR-MS (ES, m/z) calculated for C32H37N6O3Cl2 [(M+H)+] 623.2299, observed 623.2303.
Reaction SMILES: [CH3:1][C:2]([Si:5](Cl)([CH3:7])[CH3:6])([CH3:4])[CH3:3].[CH3:9][O:10][C:11](=[O:29])[CH:12]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:13][CH:14]1[CH2:19][CH2:18][CH:17]([OH:20])[CH2:16][CH2:15]1.N1C=CN=C1>ClCCl>[CH3:9][O:10][C:11]([C@@H:12]([NH:21][C:22](=[O:23])[O:24][C:25]([CH3:27])([CH3:26])[CH3:28])[CH2:13][CH:14]1[CH2:19][CH2:18][CH:17]([O:20][Si:5]([C:2]([CH3:4])([CH3:3])[CH3:1])([CH3:7])[CH3:6])[CH2:16][CH2:15]1)=[O:29]
Reactant: COC(=O)C(CC1CCC(O)CC1)NC(=O)OC(C)(C)C
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: ClCCl
Product: COC(=O)[C@H](CC1CCC(O[Si](C)(C)C(C)(C)C)CC1)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 5 h
Yield: 90.2 %

Procedure:
To a solution of TBSCl (12.7 g, 85 mmol) in dichloromethane (20 mL) was added dropwise a mixture of 2-tert-butoxycarbonylamino-3-(4-hydroxy-cyclohexyl)propionic acid methyl ester (17 g, 56 mmol) and imidazole (7.68 g, 113 mmol) in dichloromethane (200 mL) at 0° C. After stirring at rt for 5 h, the reaction mixture was washed with water and brine. The organic layer was dried over Na2SO4 and concentrated to give tert-butyl (S)-1-(methoxycarbonyl)-2-(4-(t-butyldimethylsilyloxy)cyclohexyl)ethylcarbamate (21 g, 91%) that was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ 0.08 (d, 6H), 0.89 (d, 9H), 1.45 (s, 9H), 1.51 (m, 4H), 1.58 (m, 1H), 1.68 (t, 4H), 1.85 (d, 1H) 3.71 (d, 3H), 3.91 (m, 1H), 4.34 (m, 1H), 4.86 (m, 1H).
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[C:11]([C:18]#[N:19])[CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[C:18]([C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:10]=1[CH2:9][NH:8][CH2:17][CH2:16]2)#[N:19]
Reactant: CC(C)(C)OC(=O)N1CCc2cccc(C#N)c2C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N#Cc1cccc2c1CNCC2
Temperature: 40 °C
Reaction time: 16 h
Yield: 105.4 %

Procedure:
A mixture of 2-t-butyloxycarbonyl-8-cyano-1,2,3,4-tetrahydroisoquinoline (1.4 g, 5.4 mmol) and trifluoroacetic acid (2 ml) in dichloromethane (20m1) was stirred at 40° C. for 16 h. Mixture was evaporated in vacuo and the resulting residue partitioned between dichloromethane and saturated potassium carbonate solution. The aqueous layer was extracted with more dichloromethane (2×100 ml). The combined organic extracts were dried (Na2SO4) and evaporated in vacuo to afford the desired product as an amber oil (0.9 g, 100%).
Reaction SMILES: [N:1]([CH2:4][C:5]([NH:7][CH2:8][CH:9]1[O:15][CH:14]2[N:11]([C:12](=[O:16])[CH2:13]2)[CH2:10]1)=[O:6])=[N+:2]=[N-:3].[CH3:17][C:18](C)=O>>[N:1]1([CH2:4][C:5]([NH:7][CH2:8][CH:9]2[O:15][CH:14]3[N:11]([C:12](=[O:16])[CH2:13]3)[CH2:10]2)=[O:6])[CH:18]=[CH:17][N:3]=[N:2]1
Reactant: CC(C)=O
Reactant: [N-]=[N+]=NCC(=O)NCC1CN2C(=O)CC2O1
Product: O=C(Cn1ccnn1)NCC1CN2C(=O)CC2O1
Temperature: 65 °C
Yield: 69 %

Procedure:
150 mg of (3RS,5RS)-3-[N-(Azidoacetyl)aminomethyl]-4-oxa-1-azabicyclo[3.2.0]heptan-7-one was dissolved in 10 ml of Acetone and Acetylene was bubbled at -78° C. for 5 minutes. The reaction mixture was heated at 60-70° C. in seal tube for 17 hrs. After reaction completed, solvent was removed in vacuo and the residue was purified by silicagel column chromatography (Ethyl acetate+Acetone 3:1). The title compound was obtained as oil.
Reaction SMILES: [CH:1]1([NH:4][C:5](=[O:36])[NH:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][C@@H:30]4[CH3:35])[C:16]4[CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][C:17]=4[N:18]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O.CC1C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl.CO>[CH:1]1([NH:4][C:5]([NH:6][C:7]2[CH:8]=[CH:9][C:10]([C:13]3[N:14]=[C:15]([N:29]4[CH2:34][CH2:33][O:32][CH2:31][C@@H:30]4[CH3:35])[C:16]4[CH2:21][NH:20][CH2:19][C:17]=4[N:18]=3)=[CH:11][CH:12]=2)=[O:36])[CH2:2][CH2:3]1
Reactant: C[C@H]1COCCN1c1nc(-c2ccc(NC(=O)NC3CC3)cc2)nc2c1CN(C(=O)OC(C)(C)C)C2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@H]1COCCN1c1nc(-c2ccc(NC(=O)NC3CC3)cc2)nc2c1CNC2
Temperature: 20 °C
Reaction time: 8 h
Yield: 58.3 %

Procedure:
To a stirred solution of (S)-tert-butyl 2-(4-(3-cyclopropylureido)phenyl)-4-(3-methylmorpholino)-5H-pyrrolo[3,4-d]pyrimidine-6(7H)-carboxylate (0.99 g, 1.99 mmol) in DCM (5 mL) was added TFA (2.5 mL) and stirred at room temperature (20° C.) overnight. The reaction mixture was diluted with methanol and adsorbed onto a mp-TsOH cartridge (2.5 g, 3 mmol/g). The cartridge was rinsed with MeOH (3 column volumes) and the product was eluted with 7M NH3 in MeOH. The basic fractions were concentrated in vacuo to leave a pale orange solid (0.46 g, 1.16 mmol, 58% yield).
Reaction SMILES: [C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[SH:4].[C:11]1(O)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.P(Cl)(Cl)(Cl)=O.Cl>O>[C:1]([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[SH:4]
Reactant: O=C(O)c1ccccc1S
Reactant: Oc1ccccc1
Agent: Cl
Solvent: O=P(Cl)(Cl)Cl
Solvent: O
Product: O=C(Oc1ccccc1)c1ccccc1S
Reaction time: 0.5 h

Procedure:
In a 250 ml three-necked flask a mixture of 69.4 g (0.45 mol) of thiosalicylic acid and 42.3 g (0.45 mol) of phenol is melted at 135° C. with stirring. Then, at 125°-130° C., 24.5 g (0.16 mol) of phosphorus oxychloride are added dropwise, HCl being liberated. When the addition is complete (about 15 min.) stirring is carried out for 30 minutes. The resulting dark-brown clear solution is stirred into 500 ml of water, a brown oil separating. This oil is taken up in ethyl acetate. The organic phase is extracted three times by shaking with soda solution, washed with water, dried and concentrated to a residue. The residue, which still contains phenol, is purified by distillation. The crude product is recrystallised from 250 ml of absolute methanol in the presence of activated carbon. The product is obtained in the form of colourless crystals having a melting point of 89° C. The yield is 36.0 g (=35% of the theoretical amount).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:17]3[S:16][N:15]=[CH:14][C:13]=3[CH:12]=[CH:11][C:10]=2[C:18]([OH:20])=O)=[C:4]([F:21])[CH:3]=1.C(N(C(C)C)CC)(C)C.[CH:31]([O:33][CH2:34][CH2:35][O:36][NH2:37])=[CH2:32].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.C(OCC)(=O)C>[CH:31]([O:33][CH2:34][CH2:35][O:36][NH:37][C:18]([C:10]1[CH:11]=[CH:12][C:13]2[CH:14]=[N:15][S:16][C:17]=2[C:9]=1[NH:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[F:21])=[O:20])=[CH2:32]
Reactant: O=C(O)c1ccc2cnsc2c1Nc1ccc(Br)cc1F
Reactant: C=COCCON
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C=COCCONC(=O)c1ccc2cnsc2c1Nc1ccc(Br)cc1F
Temperature: 25 °C
Reaction time: 18 h
Yield: 36.8 %

Procedure:
To a solution of 7-(4-bromo-2-fluoro-phenylamino)-benzo[d]isothiazole-6-carboxylic acid (210 mg, 0.57 mmol) and diisopropylethylamine (0.29 mL, 1.71 mmol) in DMF (2 mL) were added O-(2-vinyloxy-ethyl)-hydroxylamine (117 mg, 1.14 mmol), EDCI (220 mg, 1.14 mmol) and HOBt (154 mg, 1.14 mmol). The reaction mixture was stirred for 18 hours at room temperature, diluted with ethyl acetate and washed with water, a saturated aqueous solution of sodium hydrogen carbonate then brine before being dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0% to 100%, TBME in cyclohexane) to afford the title compound as a yellow oil (95 mg, 37%). LCMS (method B): RT=3.90 min, [M+H]+=452/454.
Reaction SMILES: BrC1N=C([Si](C)(C)C)SC=1.C([Li])CCC.C([Sn](Cl)(CCCC)CCCC)CCC.C[Si](C)(C)[C:32]1[S:33][CH:34]=[C:35]([Sn:37]([CH2:46][CH2:47][CH2:48][CH3:49])([CH2:42][CH2:43][CH2:44][CH3:45])[CH2:38][CH2:39][CH2:40][CH3:41])[N:36]=1>CCOCC.C(Cl)(Cl)Cl.CO>[CH2:46]([Sn:37]([CH2:38][CH2:39][CH2:40][CH3:41])([CH2:42][CH2:43][CH2:44][CH3:45])[C:35]1[N:36]=[CH:32][S:33][CH:34]=1)[CH2:47][CH2:48][CH3:49]
Reactant: CCCC[Sn](CCCC)(CCCC)c1csc([Si](C)(C)C)n1
Agent: CCCC[Sn](Cl)(CCCC)CCCC
Agent: C[Si](C)(C)c1nc(Br)cs1
Agent: [Li]CCCC
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Solvent: CO
Product: CCCC[Sn](CCCC)(CCCC)c1cscn1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
n-Butyllithium (1.6M, 3.1 mL, 4.94 mmol) was added to a solution of 2,4-dibromothiazole (1 g, 4.12 mmol) in anhydrous ether (25 mL) stirred at −78° C. under nitrogen. After 15 min, chlorotrimethylsilane (493 mg, 4.53 mmol) was added, then the solution was allowed to warm to room temperature, and stirred for another 1 h. The mixture was quenched, and washed with 1N sodium hydroxide, dried through MgSO4, and then the solvent was evaporated to give a brown oily residue (905 mg). The residue was purified by the distillation to give 4-bromo-2-trimethylsilylthiazole (650 mg) as a light-brown oil. Under nitrogen, the 4-bromo-2-trimethylsilylthiazole (340 mg, 1.44 mmol) was then dissolved in anhydrous ether (15 mL), and the resulting solution was stirred at −78° C. n-Butyllithium (1.5M, 1.4 mL, 2.16 mmol) was added, and the resulting solution was stirred at −78° C. for 30 minutes. Tri-n-butylstannyl chloride (703 mg, 2.16 mmol) was added, then the solution was allowed to warm to room temperature, and stirred for another 1 h. The mixture was quenched and washed with 1N sodium hydroxide, dried through MgSO4, and then the solvent was evaporated to give a brown oily residue. The residue of 2-trimethylsilyl-4-tri-n-butylstannylthiazole was passed through a column of neutral alumina eluting with a gradient of ammoniated methanol in chloroform to give the sub-title compound, 4-tri-n-butylstannylthiazole as a yellow oil (330 mg).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:14][C:15]1[C:16]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:17][C:18]2[O:22][C:21]([CH2:24][OH:25])([CH3:23])[CH2:20][C:19]=2[C:26]=1[C:27]([CH3:30])([CH3:29])[CH3:28])(=[O:13])[CH3:12].[Cl-].[NH4+]>ClCCl.C(N(CC)CC)C>[C:11]([O:14][C:15]1[C:16]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:17][C:18]2[O:22][C:21]([CH:24]=[O:25])([CH3:23])[CH2:20][C:19]=2[C:26]=1[C:27]([CH3:30])([CH3:29])[CH3:28])(=[O:13])[CH3:12]
Reactant: CC(=O)Oc1c(C(C)(C)C)cc2c(c1C(C)(C)C)CC(C)(CO)O2
Agent: O=C(Cl)C(=O)Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)Oc1c(C(C)(C)C)cc2c(c1C(C)(C)C)CC(C)(C=O)O2
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 73.6 %

Procedure:
Under a nitrogen atmosphere, 2.64 ml of oxalyl chloride was added to 40 ml of dichloromethane and the mixture was cooled to -78° C. Then, a solution of 3.62 ml of dimethyl sulfoxide in 10 ml of dichloromethane was added dropwise at -78° C. and the mixture was stirred for 30 minutes. A solution of 5.4 g of 5-acetoxy-4,6-di-t-butyl-2-hydroxymethyl-2-methyl-2,3-dihydrobenzofuran synthesized in Example 47 in 15 ml of dichloromethane was added dropwise and the mixture was stirred again at -78° C. for 1 hour. The mixture was combined with 15.3 ml of triethylamine and allowed to warm to room temperature over 1 hour. After reaction, the reaction solution was combined with a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The concentrate was purified by silica gel column chromatography eluting with n-hexane containing 20% ethyl acetate to give 3.95 g of 5-acetoxy-4,6-di-t-butyl-2-formyl-2-methyl-2,3-dihydrobenzofuran (rotamer mixture) as a white crystal (yield 71%).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([B:6]2[O:14][C:11]([CH3:13])([CH3:12])[C:8]([CH3:10])([CH3:9])[O:7]2)[CH:3]=[N:2]1.Cl.Cl[CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][N:20]1[CH3:25]>C(N(CC)CC)C>[CH3:25][N:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH:19]1[CH2:18][CH2:17][N:2]1[CH:3]=[C:4]([B:6]2[O:7][C:8]([CH3:9])([CH3:10])[C:11]([CH3:13])([CH3:12])[O:14]2)[CH:5]=[N:1]1
Reactant: CN1CCCCC1CCCl
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Agent: Cl
Solvent: CCN(CC)CC
Product: CN1CCCCC1CCn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Temperature: 90 °C

Procedure:
The title compound was prepared from pyrazole-4-boronic acid pinacol ester and 2-(2-chloroethyl)-1-methylpiperidine hydrochloride according to Method AC (heating to 90° C. for 6 days before addition of further 2-(2-chloroethyl)-1-methylpiperidine hydrochloride and triethylamine, then heating to 90° C. for a further 3 days) and was isolated as a brown oil (quantitative). LCMS (ES+) 320 (M+H)+, RT 1.85 minutes (Method 1).
Reaction SMILES: [C:1]([OH:12])(=[O:11])[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[C:13]([Cl:16])(Cl)=[O:14].[Cl:17][CH2:18]CCl>N1C=CC=CC=1>[C:6]([O:14][CH3:13])(=[O:8])[C:5]1[CH:4]=[CH:3][C:2]([C:1]([O:12][CH3:18])=[O:11])=[CH:10][CH:9]=1.[C:13]([Cl:16])(=[O:14])[C:5]1[CH:9]=[CH:10][C:2]([C:1]([Cl:17])=[O:12])=[CH:3][CH:4]=1
Reactant: O=C(Cl)Cl
Reactant: ClCCCl
Reactant: O=C(O)c1ccc(C(=O)O)cc1
Solvent: c1ccncc1
Product: COC(=O)c1ccc(C(=O)OC)cc1
Product: O=C(Cl)c1ccc(C(=O)Cl)cc1

Procedure:
Following the general procedure of Example 1 for the preparation of the diacid chloride, 10.31 parts of terephthalic acid were added to a mixture of 10.57 parts pyridine and 14.5 parts phosgene in 200 parts dry 1,2-dichloroethane at 25° to 30° C. The ratio of equivalents of pyridine base/COOH acid group was 1.08. After carrying out the reaction and esterifying the resulting diacid chloride by the procedure described in Example 1, a 95% yield of theory of dimethyl terephthalate was obtained corresponding to a 95% yield of theory of terephthaloyl chloride formed initially in the reaction.
Reaction SMILES: [H-].[Na+].[N+:3]([C:6]1[C:7]([OH:16])=[C:8]([O:14][CH3:15])[CH:9]=[C:10]([CH:13]=1)[CH:11]=[O:12])([O-:5])=[O:4].[CH2:17](I)[CH2:18][CH3:19].O>CN(C)C=O>[CH3:15][O:14][C:8]1[CH:9]=[C:10]([CH:13]=[C:6]([N+:3]([O-:5])=[O:4])[C:7]=1[O:16][CH2:17][CH2:18][CH3:19])[CH:11]=[O:12]
Reactant: CCCI
Reactant: COc1cc(C=O)cc([N+](=O)[O-])c1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCOc1c(OC)cc(C=O)cc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A mixture of sodium hydride (6.09 g, 152.3 mmole) in 20 mL of dry dimethylformamide (DMF) was cooled to 0° C. and then 5-nitrovanillin (25 g, 126.8 mmole) in 41 mL of DMF was added dropwise. After 30 minutes, propyl iodide (25.87 g, 152.0 mmole) was added dropwise at 0° C. When the addition was completed, the reaction was maintained at room temperature for 2 hours and then stirred overnight at 70° C. Water was added, and-the solution extracted with ethyl ether, washed with 10% NaOH, dried over MgSO4, filtered and then evaporated in vacuo to an oil (19 g, 62.7%).
Reaction SMILES: [CH3:1][C:2]([CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])=[CH2:3].ClC1C=CC=C(C(OO)=[O:17])C=1>C(Cl)Cl>[CH3:3][C:2]1([CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[O:17][CH2:1]1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=C(C)CCCCC
Solvent: ClCCl
Product: CCCCCC1(C)CO1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 40.6 %

Procedure:
To a solution of 2-methyl-1-heptene 4 (17 g, 0.15 mol) in methylene chloride (300 mL) at 0° C. was added meta-chloroperbenzoic acid (37 g, 0.18 mol) in portions. The reaction mixture was stirred at 0° C. for 30 minutes, then at room temperature overnight. It was cooled in an ice bath and then filtered. The filtrate was washed with 5% sodium hydroxide, saturated sodium chloride and dried over magnesium sulfate; 7.8 g of 2-methyl-1-heptene oxide 5 was obtained after HPLC purification.
Reaction SMILES: Br[CH:2]=[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([O:13][CH3:14])=[O:12])=[CH:5][CH2:4]1.[C:19]1(=[O:29])[NH:23][C:22](=[O:24])[C:21]2=[CH:25][CH:26]=[CH:27][CH:28]=[C:20]12.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:11]([C:10]1[CH:15]=[CH:16][CH:17]=[CH:18][C:9]=1[C:6]1[CH:7]=[CH:8][C:3]([CH2:2][N:23]2[C:22](=[O:24])[C:21]3=[CH:25][CH:26]=[CH:27][CH:28]=[C:20]3[C:19]2=[O:29])=[CH:4][CH:5]=1)([O:13][CH3:14])=[O:12]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: COC(=O)c1ccccc1C1=CCC(=CBr)C=C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1ccccc1-c1ccc(CN2C(=O)c3ccccc3C2=O)cc1
Yield: 7.4 %

Procedure:
Methyl 2-[4-(bromomethylene)phenyl]benzoate (1.22 g, 0.04 mole), phthalimide (0.59 g, 0.04 mole), and potassium carbonate (0.55 g, 0.04 mole) are combined in 120 mL acetonitrile. The mixture is heated at reflux for 24 hours. At that time the mixture is filtered through celite and rotovapped to a residue. The residue is crystallized from ethyl acetate to afford 1.1 g (71%) of the title compound as a tan solid mp 148°-150° C. 1H NMR (CDCl3) 7.9-7.1 (12H, m); 4.92 (2H, s); 3.63 (3H, s). Mass Spec. (DCl) m/z 372 (M+H). Analysis--calc'd for C23H17NO4.1/2 H2O: C, 72.62; H, 4.77: N, 3.68; found: C, 72.88; H, 4.55; N, 3.77.
Reaction SMILES: [CH2:1]([N:4]1[C:8]2[CH:9]=[C:10]([N+:14]([O-])=O)[C:11]([F:13])=[CH:12][C:7]=2[N:6]=[C:5]1[C:17]([F:20])([F:19])[F:18])[C:2]#[CH:3].C(OCC)(=O)C.O>C(O)(=O)C.[Fe]>[CH2:1]([N:4]1[C:8]2[CH:9]=[C:10]([NH2:14])[C:11]([F:13])=[CH:12][C:7]=2[N:6]=[C:5]1[C:17]([F:19])([F:20])[F:18])[C:2]#[CH:3]
Reactant: C#CCn1c(C(F)(F)F)nc2cc(F)c([N+](=O)[O-])cc21
Agent: [Fe]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: C#CCn1c(C(F)(F)F)nc2cc(F)c(N)cc21
Temperature: 60 °C
Yield: 101.1 %

Procedure:
A stirred mixture of 1.5 grams (0.005 mole) of 1-(2-propyn-1-yl)-2-trifluoromethyl-5-fluoro-6-nitrobenzimidazole, 1.0 gram (0.018 mole) of iron powder, and 10 mL of ethyl acetate in 35 mL of acetic acid was heated at 60° C. for two hours. The reaction mixture was then poured into water, and the mixture was extracted thoroughly with portions of ethyl acetate. The combined extracts were washed with aqueous solutions saturated with sodium bicarbonate and sodium chloride. The organic layer was dried with sodium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residual oil, which was triturated with water, and the resultant solid collected by filtration. The solid was dried, yielding 1.3 grams of 1-(2-propyn-1-yl)-2-trifluoromethyl-5-fluoro-6-aminobenzimidazole. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.CO[C:13]([C:15]1[CH:20]=[C:19](OC)[C:18]([CH2:23][C:24]2[C:25]([NH2:31])=[N:26][C:27]([NH2:30])=[N:28][CH:29]=2)=[C:17](OC)[CH:16]=1)=[O:14].[CH3:34][OH:35].O.[O:37]1CCOC[CH2:38]1>>[NH2:30][C:27]1[N:26]=[C:25]([NH2:31])[C:24]([CH2:23][C:18]2[CH:17]=[C:16]([O:37][CH3:38])[C:15]([CH2:13][OH:14])=[C:20]([O:35][CH3:34])[CH:19]=2)=[CH:29][N:28]=1
Reactant: C1COCCO1
Reactant: CO
Reactant: COC(=O)c1cc(OC)c(Cc2cnc(N)nc2N)c(OC)c1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: O
Product: COc1cc(Cc2cnc(N)nc2N)cc(OC)c1CO
Temperature: 30 °C
Reaction time: 1 h

Procedure:
135 Ml. of about 15% diisobutylaluminum hydride solution in dioxane were added dropwise within 30 minutes at 50°C. under nitrogen and exclusion of moisture to a solution of 4.45 g. of α-(2,4-diamino-5-pyrimidinyl)-2,6-dimethoxy-p-toluic acid methyl ester in 400 ml. of absolute dioxane. The resulting suspension was stirred at 50° for 1 hour. After cooling to 30°C., the reaction mixture was treated with a mixture of 25 ml. of methanol, 5 ml. of water and 50 ml. of dioxane and stirred at 50° for an additional 2 hours. The solid material was separated and rejected, and the filtrate was evaporated to dryness. After recrystallization from about 20 ml. of methanol, the residue yielded 4-[ (2,4-diamino-5-pyrimidinyl)-methyl] -2,6-dimethoxybenzyl alcohol having a m.p. of 227°-228°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][CH:20]=1)[CH:6](O)[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][CH:8]=1.[ClH:21]>C(OCC)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][CH:20]=1)[CH:6]([Cl:21])[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][CH:8]=1
Reactant: Cl
Reactant: COc1cccc(C(O)c2cccc3ccccc23)c1
Solvent: CCOCC
Product: COc1cccc(C(Cl)c2cccc3ccccc23)c1
Temperature: 25 °C
Yield: 72 %

Procedure:
To a solution of 3-methoxy-α-(1-naphthyl)benzyl alcohol (2.5 g, 9.5 mmol) in diethyl ether (5 mL) was added 35% hydrochloric acid (10 mL) at 0° C. The reaction mixture was warmed to r.t. in 1 h, and then extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with aqueous NH4Cl solution and brine, dried over MgSO4. Evaporation of solvents gave 3-methoxy-α-(1-naphthyl)benzyl chloride (1.94 g, 72%). GC-MS (Rt =10.30 min) 282 (M+), 247, 232, 215, 202, 189, 163, 151, 139, 123, 101.