Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][CH:2]([CH3:11])[CH2:3][C@@H:4]1[NH:9][C:8](=[O:10])[CH2:7][O:6][CH2:5]1.Cl.[CH2:13]([O:20][C:21](Cl)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[OH-:24].[Na+]>O>[CH3:1][CH:2]([CH3:11])[CH2:3][C@H:4]([NH:9][C:21]([O:20][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:22])[CH2:5][O:6][CH2:7][C:8]([OH:24])=[O:10]
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CC(C)C[C@H]1COCC(=O)N1
Reactant: [OH-]
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CC(C)C[C@@H](COCC(=O)O)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
(S)-5-(2-Methylpropyl)-3-morpholinone, 3 g (0.019 mol), is suspended in a solution of 50 ml of concentrated hydrochloric acid and 50 ml of water, refluxed for four hours, cooled to room temperature, and extracted with 200 ml of dichloromethane. The aqueous layer is separated, evaporated in vacuo, the residue dissolved in 200 ml of water and the pH adjusted with a 10% aqueous solution of sodium hydroxide to pH 10-10.5. The solution is cooled to 5° C. and 3.73 g (0.022 mol) of benzylchloroformate is added dropwise while the pH is maintained at pH 10 with a 10% aqueous solution of sodium hydroxide. The mixture is stirred one hour, extracted with 100 ml of diethylether, the aqueous layer is separated and the pH is adjusted to pH 3-4 by the addition of a 10% aqueous solution of hydrochloric acid. The mixture is extracted with dichloromethane, 3×200 ml. The dichloromethane layer is separated, washed with a saturated aqueous solution of sodium chloride, 3×200 ml, separated, dried over sodium sulfate, evaporated and the residue is purified by chromatography using silica gel and eluting with dichloromethane-methanol (95:5) to give (S)-[[4-methyl2[[(phenylmethoxy)carbonyl]amino]pentyl]oxy]acetic acid, 5 g; [α]D25 -30.5 (c 0.55, methanol).
Reaction SMILES: I[C:2]1[CH:26]=[CH:25][CH:24]=[CH:23][C:3]=1[CH2:4][O:5][NH:6][C:7](=[O:22])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][CH2:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=1.[C:27]([O:30][CH2:31][CH2:32][O:33][CH2:34][C:35]#[CH:36])(=[O:29])[CH3:28]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[N:19]1[CH:20]=[CH:21][C:16]([CH2:15][NH:14][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[C:7]([NH:6][O:5][CH2:4][C:3]2[CH:23]=[CH:24][CH:25]=[CH:26][C:2]=2[C:36]#[C:35][CH2:34][O:33][CH2:32][CH2:31][O:30][C:27](=[O:29])[CH3:28])=[O:22])=[CH:17][CH:18]=1
Reactant: C#CCOCCOC(C)=O
Reactant: O=C(NOCc1ccccc1I)c1ccccc1NCc1ccncc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Product: CC(=O)OCCOCC#Cc1ccccc1CONC(=O)c1ccccc1NCc1ccncc1

Procedure:
The same procedure was used as described for the preparation of example 365, but without addition of tetrabutylammonium iodide. Starting materials: N-(2-Iodo-benzyloxy)-2-[(pyridin-4-ylmethyl)-amino]-benzamide (see example 360) and 2-(prop-2-ynyloxy)ethyl acetate (Maybridge).
Reaction SMILES: C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:15][C:16]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][CH:38]=O)=[CH:32][C:17]=1[C:18]([NH:20][CH2:21][C:22]12[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH2:23]1)[CH2:29]2)=[O:19].[OH:40][C@@H:41]([CH3:44])[CH2:42][NH2:43]>ClCCl>[ClH:15].[Cl:15][C:16]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][CH2:38][NH:43][CH2:42][C@@H:41]([OH:40])[CH3:44])=[CH:32][C:17]=1[C:18]([NH:20][CH2:21][C:22]12[CH2:31][CH:26]3[CH2:27][CH:28]([CH2:30][CH:24]([CH2:25]3)[CH2:23]1)[CH2:29]2)=[O:19]
Reactant: O=CCCc1ccc(Cl)c(C(=O)NCC23CC4CC(CC(C4)C2)C3)c1
Reactant: C[C@H](O)CN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: C[C@H](O)CNCCCc1ccc(Cl)c(C(=O)NCC23CC4CC(CC(C4)C2)C3)c1
Product: Cl
Yield: 60.1 %

Procedure:
Sodium triacetoxyborohydride (0.6 g) was added to a solution of 2-chloro-5-(3-oxopropyl)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.5 g, Example 14b) and (S)-2-hydroxypropylamine (0.31 g) in dichloromethane (5 ml). After 24 h the crude reaction mixture was purified by flash chromatography (eluting with 5-20% methanol in dichloromethane +1% ammonia) and the hydrochloride salt precipitated from ether/methanol 19: 1, to afford the title compound as a white solid (0.19 g).
Reaction SMILES: O.[OH-].[Na+].C(=O)CCCC.C1(=O)CCCC1.O[CH:17]([CH:22]1[CH2:26][CH2:25][CH2:24][C:23]1=[O:27])[CH2:18][CH2:19][CH2:20][CH3:21]>>[CH:17](=[C:22]1[CH2:26][CH2:25][CH2:24][C:23]1=[O:27])[CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCC(O)C1CCCC1=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: O=C1CCCC1
Solvent: CCCCC=O
Product: CCCCC=C1CCCC1=O
Temperature: 15 °C
Yield: 2.2 %

Procedure:
A 100 mL four-necked flask was charged with 16.6 g (0.92 mol) of water and 0.16 g (0.004 mol) of sodium hydroxide. After cooling the contents of the flask to 15° C. under stirring, a mixed solution containing 61.3 g (0.71 mol) of valeraldehyde (acid value: 1.5 mg-KOH/g) and 237.8 g (2.83 mol) of cyclopentanone, and 36.0 g of a sodium hydroxide aqueous solution (concentration of sodium hydroxide: 0.36% by mass) were added dropwise into the flask over 6 h. While dropping, the resulting reaction mixture was withdrawn from the flask at a rate 1.4 times the dropping rate, and introduced into a dropping funnel (separator) to separate the reaction mixture into an organic layer and a water layer. The water layer separated as a lower layer of the reaction mixture was returned to the flask. Whereas, the organic layer separated as an upper layer of the reaction mixture was collected every one hour, and each part of the organic layer collected every one hour was subjected to gas chromatography. After completion of the dropping, the reaction mixture in the flask was separated into the respective layers, and each of the thus separated organic and water layers was analyzed by gas chromatography. As a result, it was confirmed that the organic layer contained 3.06 g (0.036 mol) of valeraldehyde, 106.5 g (0.63 mol) of 2-(1-hydroxy-n-pentyl)cyclopentanone and 2.13 g (0.014 mol) of pentylidene cyclopentanone (conversion rate of valeraldehyde: 95.0%; yield: 89.9%).
Reaction SMILES: [N:1]([CH2:4][CH2:5][CH2:6][S:7][C:8]1[C:16]2[C:15](=[O:17])[N:14]([CH3:18])[C:13](=[O:19])[N:12]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:11]=2[S:10][C:9]=1[CH2:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1)=[N+]=[N-].C(S)CCS.C(N(CC)CC)C.[BH4-].[Na+]>ClCCl.C(O)(C)C>[NH2:1][CH2:4][CH2:5][CH2:6][S:7][C:8]1[C:16]2[C:15](=[O:17])[N:14]([CH3:18])[C:13](=[O:19])[N:12]([CH2:20][CH:21]([CH3:22])[CH3:23])[C:11]=2[S:10][C:9]=1[CH2:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1
Reactant: CC(C)Cn1c(=O)n(C)c(=O)c2c(SCCCN=[N+]=[N-])c(Cc3cccc4ccccc34)sc21
Agent: SCCCS
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)Cn1c(=O)n(C)c(=O)c2c(SCCCN)c(Cc3cccc4ccccc34)sc21
Reaction time: 8 h
Yield: 45.1 %

Procedure:
5-[(3-Azidopropyl)thio]-3-methyl-1-(2-methylpropyl)-6-(1-naphthalenylmethyl)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (656 mg), 1,3-propanedithiol (100 μl) and triethylamine (400 μl) were dissolved in a mixture of dichloromethane (3 ml) and isopropanol (5 ml). Sodium borohydride (78 mg) was added and the mixture was stirred overnight. The solvents were removed by evaporation then dilute hydrochloric acid was added dropwise until effervescence ceased. The solution was made alkaline with aqueous sodium hydroxide and then extracted with dichloromethane (four times). The extracts were dried, filtered and evaporated. Purification by HPLC (ethanol:dichloromethane 5-40: 95-60) followed by trituration with ether-cyclohexane gave the title compound (280 mg).
Reaction SMILES: [Li]C(C)(C)C.[CH3:6][Si:7]([CH3:20])([CH3:19])[CH2:8][CH2:9][O:10][CH2:11][O:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1.Cl[Si:22]([CH3:25])([CH3:24])[CH3:23].O>CCOCC>[CH3:23][Si:22]([CH3:25])([CH3:24])[C:18]1[CH:17]=[CH:16][N:15]=[CH:14][C:13]=1[O:12][CH2:11][O:10][CH2:9][CH2:8][Si:7]([CH3:20])([CH3:19])[CH3:6]
Reactant: C[Si](C)(C)CCOCOc1cccnc1
Reactant: C[Si](C)(C)Cl
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Solvent: O
Product: C[Si](C)(C)CCOCOc1cnccc1[Si](C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 60 %

Procedure:
Add t-BuLi dropwise to a −78° C. solution of 3-(2-trimethylsilanyl-ethoxymethoxy)-pyridine (1.98 g, 8,8 mmol) in Et2O (25 mL, freshly distilled over Na0). After 1 hour, add chlorotrimethylsilane (1.33 mL, 10.5 mmol) dropwise and allow reaction to warm slowly to RT. After 1.5 hours, add water (5 mL) dropwise to quench. Wash with saturated NaHCO3 solution and brine. Dry the combined organic layers over MgSO4 and concentrate. Purify the residue by flash chromatography on silica gel eluting with 0-30% EtOAc/hexanes to afford the title compound (1.57 g, 60%) as yellow oil. MS(IS) 298 (M+1). TLC: Rf=0.38 (35% EtOAc/hexanes).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10](Cl)[N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:13][S-:14].[Na+]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([S:14][CH3:13])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)c1cc(Cl)nc(Cl)c1
Reactant: C[S-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(Cl)nc(SC)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 93.1 %

Procedure:
Methyl 2,6-dichloroisonicotinate (300 mg, 1.45 mmol) was dissolved in anhydrous DMF. Sodium thiomethoxide (102 mg, 1.45 mmol) was added and the mixture was stirred at room temperature for 4 h. The mixture was diluted with EtOAc and washed with water (×3), brine (×1) and dried over sodium sulfate and concentrated in vacuo to afford title compound (294 mg).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[C:12]([C:15](=[O:18])[CH2:16][Cl:17])[CH:11]=[CH:10][C:9]=2[OH:19])=[O:5])[CH3:2].[CH2:20]([O:22][C:23](=[O:36])[CH2:24][C:25]([NH:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)([CH3:27])[CH3:26])[CH3:21]>>[ClH:17].[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[C:12]([C:15](=[O:18])[CH2:16][N:28]([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:25]([CH3:26])([CH3:27])[CH2:24][C:23]([O:22][CH2:20][CH3:21])=[O:36])[CH:11]=[CH:10][C:9]=2[OH:19])=[O:5])[CH3:2]
Reactant: CCOC(=O)CC(C)(C)NCc1ccccc1
Reactant: CCOC(=O)c1cc2c(C(=O)CCl)ccc(O)c2[nH]1
Product: CCOC(=O)CC(C)(C)N(CC(=O)c1ccc(O)c2[nH]c(C(=O)OCC)cc12)Cc1ccccc1
Product: Cl
Yield: 15.9 %

Procedure:
Under the conditions of Example 28, 2.57 g of 4-chloroacetyl-7-hydroxyindole-2-carboxylic acid ethyl ester is reacted with 2.35 g of 3-benzylamino-3-methylbutyric acid ethyl ester and worked up, yielding 0.75 g of 4-[N-benzyl-N-(2-ethoxycarbonyl-1,1-dimethylethyl)aminoacetyl]-7-hydroxyindole-2-carboxylic acid ethyl ester hydrochloride, decomposition point 210°-212° C.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][CH2:3]1.[H-].[Na+].[CH3:17][C:18]1[NH:19][C:20]([CH3:40])=[CH:21][C:22]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32](F)=[CH:31][CH:30]=2)[N:24]=1.O>CN(C)C=O>[CH3:17][C:18]1[NH:19][C:20]([CH3:40])=[CH:21][C:22]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:32]([O:1][CH:2]3[CH2:7][CH2:6][N:5]([CH2:8][C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[CH2:4][CH2:3]3)=[CH:31][CH:30]=2)[N:24]=1
Reactant: OC1CCN(Cc2ccccc2)CC1
Reactant: Cc1cc(-c2cccc(-c3ccc(F)c4ccccc34)n2)c(C)[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cc(-c2cccc(-c3ccc(OC4CCN(Cc5ccccc5)CC4)c4ccccc34)n2)c(C)[nH]1
Temperature: 70 °C
Yield: 317.3 %

Procedure:
To a 20 mL round-bottomed flask equipped with condenser and N2 inlet were added 121 mg (0.633 mml) 4-hydroxy-N-benzylpiperidine and 5 mL dry dimethylformamide, followed by 32 mg (0.791 mmol) sodium hydride (60% in oil). The reaction was heated to 70° C. to ensure complete formation of the alkoxide, and then 100 mg (0.316 mmol) 2-(2,5-dimethylpyrrolyl)-6-(4-fluoro-naphth-1-yl)pyridine in 2 mL dry dimethylformamide was added, and the reaction was heated at 80° C. for 10 min. The reaction was cooled, poured into water, and extracted into ethyl acetate. After combining with another run on a larger scale, the combined organic layer was washed with brine, dried over sodium sulfate, and evaporated. The residue was chromatographed on silica gel using methanol/methylene chloride as eluant to afford 489 mg (54%) of an oil.
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].Cl[C:6]1[CH:11]=[C:10]([CH3:12])[N:9]=[C:8]2[C:13]([CH3:16])=[N:14][NH:15][C:7]=12>>[CH2:1]([NH:4][C:6]1[CH:11]=[C:10]([CH3:12])[N:9]=[C:8]2[C:13]([CH3:16])=[N:14][NH:15][C:7]=12)[CH:2]=[CH2:3]
Reactant: Cc1cc(Cl)c2[nH]nc(C)c2n1
Reactant: C=CCN
Product: C=CCNc1cc(C)nc2c(C)n[nH]c12

Procedure:
The above compound was prepared from allylamine and 7-chloro-3,5-dimethyl-1H-pyrazolo[4,3-b]pyridine in an analogous manner to the preparation of Example 2 giving a pale yellow solid, m.p. 196°-198°.
Reaction SMILES: C(O)C[CH2:3][CH2:4][OH:5].C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC.C1C(CC2C=CC([N:57]=[C:58]=[O:59])=CC=2)=CC=C([N:60]=[C:61]=[O:62])C=1.CCCCO[C@H](CO)CC.C[N:74]1CCCC1=O>C(OCC)C.CO>[NH2:57][C:58]([O:5][CH2:4][CH3:3])=[O:59].[NH2:74][C:61]([NH2:60])=[O:62]
Reactant: CN1CCCC1=O
Reactant: OCCCCO
Reactant: O=C=Nc1ccc(Cc2ccc(N=C=O)cc2)cc1
Agent: CCCCCCCCCCCC(=O)[O-]
Agent: CCCCO[C@@H](CC)CO
Agent: CCCC[Sn+2]CCCC
Solvent: CCOCC
Solvent: CO
Product: CCOC(N)=O
Product: NC(N)=O
Yield: 77.2 %

Procedure:
In an argon atmosphere, 1,4-butanediol (0.240 g, 2.66 mmol) and dibutyltin dilaurate (0.2 ml) were dissolved in N-methylpyrrolidinone (7.00 ml) in a three-necked flask. A solution of 4,4′-diphenylmethane diisocyanate (2.00 g, 7.99 mmol) in N-methylpyrrolidinone (7.00 ml) was slowly added dropwise to the solution at room temperature. After the completion of the dropwise addition, the solution was reacted at 50° C. for 2 hours. Thereafter, a solution of the compound (6) from Example 1 (1.69 g, 2.66 mmol) in N-methylpyrrolidinone (3.00 ml) was slowly added dropwise to the reaction solution at 0° C., followed by reaction at 0° C. for 0.5 hour. After the completion of the reaction, a solution of polytetramethylene glycol (2.66 g, 2.66 mmol) in N-methylpyrrolidinone (3.00 ml) was slowly added dropwise to the reaction solution at 0° C., followed by reaction at 50° C. overnight. The resultant reaction solution was poured into an excess of a solvent mixture (methanol:diethyl ether=1:1 (by volume)). The precipitate caused was suction filtered and dried under reduced pressure to give a segmented poly(urethane-urea) with a phosphorylcholine group represented by Formula SPUU-2 above as a brown solid (weight: 5.09 g, yield: 77.2%). The structure of the polymer was determined from the IR spectrum given below. From the 1H-NMR spectrum, the phosphorylcholine group content in the polymer SPUU-2 was found to be 19.7 mol %.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17](Br)[C:16]([CH3:20])=[CH:15][C:14]=2[C:21]#[N:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:23]1(B(O)O)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:16]([CH3:20])=[CH:15][C:14]=2[C:21]#[N:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: OB(O)c1ccccc1
Reactant: Cc1cc(C#N)c(OC2CN(C(=O)OC(C)(C)C)C2)cc1Br
Product: Cc1cc(C#N)c(OC2CN(C(=O)OC(C)(C)C)C2)cc1-c1ccccc1

Procedure:
Prepared from the title compound of Step A as described in Example 1 Step E using phenylboronic acid.
Reaction SMILES: [C-]#N.[K+].CC(C)(O)[C:6]#[N:7].[C:10]([O:14][C:15](=[O:39])[C:16]1[CH:21]=[CH:20][C:19]([C:22](=[O:37])/[CH:23]=[C:24](\[C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[C:31]([Cl:36])[CH:30]=2)/[C:25]([F:28])([F:27])[F:26])=[CH:18][C:17]=1[CH3:38])([CH3:13])([CH3:12])[CH3:11].O>C1(C)C=CC=CC=1>[C:10]([O:14][C:15](=[O:39])[C:16]1[CH:21]=[CH:20][C:19]([C:22](=[O:37])[CH2:23][C@:24]([C:6]#[N:7])([C:29]2[CH:34]=[C:33]([Cl:35])[CH:32]=[C:31]([Cl:36])[CH:30]=2)[C:25]([F:26])([F:28])[F:27])=[CH:18][C:17]=1[CH3:38])([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)(O)C#N
Reactant: Cc1cc(C(=O)/C=C(\c2cc(Cl)cc(Cl)c2)C(F)(F)F)ccc1C(=O)OC(C)(C)C
Agent: [C-]#N
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O
Product: Cc1cc(C(=O)C[C@](C#N)(c2cc(Cl)cc(Cl)c2)C(F)(F)F)ccc1C(=O)OC(C)(C)C
Temperature: 45 °C
Reaction time: 18 h
Yield: 70.5 %

Procedure:
Potassium cyanide (0.0090 g, 0.138 mmol) and acetone cyanohydrin (0.040 ml, 0.435 mmol) were added to a solution of 4-[(E)-3-(3,5-Dichloro-phenyl)-4,4,4-trifluoro-but-2-enoyl]-2-methyl-benzoic acid tert-butyl ester (0.0645 g, 0.140 mmol) in toluene (1.0 ml). To this vigorously stirred suspension was added 2,3,4,5,6-pentafluorophenyl-methyl quininium chloride (0.015 g, 0.028 mmol). The reaction mixture was stirred at 45° C. for 18 hours. At this time water was added and the reaction mixture was extracted with dichloromethane (3×). The crude product was purified by flash chromatography (0% to 5% ethyl acetate in cyclohexane) to afford 4-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester (0.048 g, 66%) as a white foam. Chiral HPLC analysis (Chiralpack IA, Heptane:2-propanol:diethylamine=95:5:0.1, 1 ml/min, retention time 6.52 minutes (major enantiomer), 6.02 minutes (minor enantiomer) indicated that the reaction proceeded with 88% enantioselectivity. 1H NMR (400 MHz, CDCl3) δ 7.89 (d, 1H), 7.78-7.72 (m, 2H), 7.48 (s, 2H), 7.46-7.42 (m, 1H), 4.17 (d, 1H), 4.02 (d, 2H), 2.62 (s, 3H), 1.62 (s, 9H)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]2[O:13][CH2:12][O:11][C:10]=12)[CH:6]=[O:7].[C:14]([Mg]Cl)#[CH:15]>C1COCC1>[OH:7][CH:6]([C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:10]2[O:11][CH2:12][O:13][C:9]=2[CH:8]=1)[C:14]#[CH:15]
Reactant: C#C[Mg]Cl
Reactant: COc1cc(C=O)cc2c1OCO2
Solvent: C1CCOC1
Product: C#CC(O)c1cc(OC)c2c(c1)OCO2

Procedure:
3-Hydroxy-3-(4-methoxy-1,3-benzodioxol-6-yl)-1-propyne was prepared according to Method A above from 3-methoxy-4,5-methylenedioxybenzaldehyde (0.721 g, 4 mmol) (Lancaster) in THF (20 mL) and ethynylmagnesium chloride (5 mmol, 10 mL, 0.5M solution in tetrahydrofuran) (Aldrich). (Yield 629 mg, 76%).
Reaction SMILES: [CH2:1]([C:16]1[CH:17]=[C:18]([OH:22])[CH:19]=[CH:20][CH:21]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].[CH3:23]S(C)=O.[OH-].[Na+].CI>O>[CH2:1]([C:16]1[CH:17]=[C:18]([O:22][CH3:23])[CH:19]=[CH:20][CH:21]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CS(C)=O
Reactant: CCCCCCCCCCCCCCCc1cccc(O)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CI
Solvent: O
Product: CCCCCCCCCCCCCCCc1cccc(OC)c1
Temperature: 25 °C
Reaction time: 7 h

Procedure:
To a two necked round bottomed flask with a reflux condenser is added 3-pentadecyl phenol, DMSO, sodium hydroxide followed by dropwise addition of alkylating agent such as methyl iodide with constant stirring at room temperature. The stirring is continued for about 6-8 hrs. The reaction mixture is then poured into deionized water and the organic matter is extracted in diethyl ether, separated the organic layer, washed with water and dried, purified to obtain 3-pentadecyl anisole.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8](Br)[C:9]=1[OH:10])[C:5]#[N:6].[N:12]([O-:14])=[O:13].[Na+].BrBr.O>C(O)(=O)C.CO>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([N+:12]([O-:14])=[O:13])[C:9]=1[OH:10])[C:5]#[N:6]
Reactant: N#Cc1cc(Br)c(O)c(Br)c1
Reactant: O=N[O-]
Agent: BrBr
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Solvent: O
Product: N#Cc1cc(Br)c(O)c([N+](=O)[O-])c1
Temperature: 50 °C
Reaction time: 8 h
Yield: 84.2 %

Procedure:
(I1B): To a suspension of 3,5-dibromo-4-hydroxybenzonitrile (2.11 g, 7.62 mmol) in acetic acid (70 mL) was added sodium nitrite (2.63 g, 38.1 mmol) in small portion, evolving bubbles and bromine were observed. After addition, the mixture was stirred at 50° C. overnight. Reaction was cooled to room temperature; water (250 mL) was added and extracted with EtOAc for two times. The combined extracts were washed with water and brine, dried over MgSO filtered and the filtrate was concentrated to give yellow orange solid. The solid was treated with small amount of MeOH, collected by filtration, rinsed with MeOH, dried to afford 1.56 g of 3-bromo-4-hydroxy-5-nitrobenzonitrile as yellow solid.
Reaction SMILES: [NH2:1][C:2]([CH3:17])([CH2:5][N:6]1[N:10]=[C:9]2[CH:11]=[CH:12][C:13]([O:15][CH3:16])=[CH:14][C:8]2=[N:7]1)[C:3]#[N:4].[F:18][C:19]([F:30])([F:29])[C:20]1[CH:28]=[CH:27][C:23]([C:24](Cl)=[S:25])=[CH:22][CH:21]=1>>[C:3]([C:2]([NH:1][C:24](=[S:25])[C:23]1[CH:22]=[CH:21][C:20]([C:19]([F:18])([F:29])[F:30])=[CH:28][CH:27]=1)([CH3:17])[CH2:5][N:6]1[N:10]=[C:9]2[CH:11]=[CH:12][C:13]([O:15][CH3:16])=[CH:14][C:8]2=[N:7]1)#[N:4]
Reactant: COc1ccc2nn(CC(C)(N)C#N)nc2c1
Reactant: FC(F)(F)c1ccc(C(=S)Cl)cc1
Product: COc1ccc2nn(CC(C)(C#N)NC(=S)c3ccc(C(F)(F)F)cc3)nc2c1

Procedure:
Using a procedure similar to that described in Example 1, except using 2-amino-3-(5-methoxy-2H-benzotriazol-2-yl)-2-methylpropionitrile (120 mg, described in Example 44) and 4-trifluoromethylthiobenzoyl chloride (0.16 mL), the title compound was isolated as a white solid (150 mg, 66%). Rf=0.3 (1:1 EA/heptane). MS (ES): M/Z [M+H]=436. 1H NMR: (400 MHz, DMSO-d6): 1.73 (s, 3H), 3.84 (s, 3H), 5.32 (d, J=13.4 Hz, 1H), 5.38 (d, J=13.4 Hz, 1H), 7.10 (dd, J=9.3, 2.3 Hz, 1H), 7.24 (d, J=2.1 Hz, 1H), 7.82 (dd, J=9.2, 0.4 Hz, 1H), 7.87 (d, J=8.6 Hz, 2H), 7.92 (d, J=8.6 Hz, 2H) and 9.00 (s, 1H). 19F NMR (376 MHz, DMSO-d6): −41.9 (s, 3F).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[N:8]([CH2:15][CH3:16])[C:7](=[O:17])[C:6](=[O:18])[NH:5]2.CO[CH:21]1[CH2:25][CH2:24][CH:23](OC)O1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C=O.C1(C)C=CC=CC=1>[CH2:15]([N:8]1[C:9]2[C:4](=[CH:3][C:2]([N:1]3[CH:21]=[CH:25][CH:24]=[CH:23]3)=[C:11]([N+:12]([O-:14])=[O:13])[CH:10]=2)[NH:5][C:6](=[O:18])[C:7]1=[O:17])[CH3:16]
Reactant: CCn1c(=O)c(=O)[nH]c2cc(N)c([N+](=O)[O-])cc21
Reactant: COC1CCC(OC)O1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: CCn1c(=O)c(=O)[nH]c2cc(-n3cccc3)c([N+](=O)[O-])cc21
Yield: 374.7 %

Procedure:
4.0 g (16 mmol) of 6-amino-1-ethyl-7-nitro-2,3(1H,4H)-quinoxalinedione, 2.4 g (18 mmol) of 2,5-dimethoxytetrahydrofuran and a spatula tip of p-toluenesulfonic acid were refluxed in a mixture of 50 ml of dimethylformamide and 50 ml of toluene with a water trap for 3 h. The mixture was then concentrated under reduced pressure, and the residue was treated with methanol. The precipitate was filtered off with suction to yield 18 g (3%) of the product.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[S:9][C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][CH:11]=1.[C:17]1(B(O)O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C>C(Cl)Cl.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH3:8][C:6]1[CH:5]=[CH:4][C:3]([S:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:12][CH:11]=2)=[C:2]([NH2:1])[CH:7]=1
Reactant: OB(O)c1ccccc1
Reactant: Cc1ccc(Sc2ccc(O)cc2)c(N)c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: Cc1ccc(Sc2ccc(Oc3ccccc3)cc2)c(N)c1
Temperature: 25 °C
Reaction time: 48 h
Yield: 15.3 %

Procedure:
The product from Example 6c (0.500 g, 1.91 mmol) was dissolved in CH2Cl2 along with phenyl boronic acid (0.701 g, 5.74 mmol), copper(II) acetate (0.659 g, 3.83 mmol), and triethylamine (0.387 g, 3.83 mmol). Stirred at room temperature for 48 h, at which time 2 more equivalents of each reagent was added. Stirred at room temperature for another 16 h at which time another 2 eq of each reagent was added. Stirred at room temperature for another 16 h. The reaction was diluted with water and extracted with ethyl acetate Dried over Na2SO4, filtered and concentrated under vacuum giving the crude product which was purified silica gel column chromatography eluting with 20% EtOAc/hexane (0.100 g, 15%). The product was reduced with SnCl2 following the procedure from Example 5I to give the title compound (90 mg, 98%).