Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[N:31]=[CH:30][C:29]([CH:32]=[O:33])=[CH:28][CH:27]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[CH3:34][Mg]Br.O>O1CCCC1>[CH:1]1([S:4]([C:7]2[CH:8]=[CH:9][C:10]([CH:13]([C:21]3[NH:25][C:24]([C:26]4[N:31]=[CH:30][C:29]([CH:32]([OH:33])[CH3:34])=[CH:28][CH:27]=4)=[CH:23][CH:22]=3)[CH2:14][CH:15]3[CH2:16][CH2:17][O:18][CH2:19][CH2:20]3)=[CH:11][CH:12]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1
Reactant: C[Mg]Br
Reactant: O=Cc1ccc(-c2ccc(C(CC3CCOCC3)c3ccc(S(=O)(=O)C4CC4)cc3)[nH]2)nc1
Solvent: C1CCOC1
Solvent: O
Product: CC(O)c1ccc(-c2ccc(C(CC3CCOCC3)c3ccc(S(=O)(=O)C4CC4)cc3)[nH]2)nc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 40 %

Procedure:
To a solution of 6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carbaldehyde (200 mg) in tetrahydrofuran (5 mL) was added methylmagnesium bromide (3M diethyl ether solution, 450 μL) at 0° C., and the mixture was stirred overnight at room temperature. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (83.0 mg, yield 40%) was obtained as a pale-yellow amorphous solid from a fraction eluted with ethyl acetate. MS: 481 (MH+).
Reaction SMILES: [CH2:1]([C:5]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]3[N:28](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:27]=[N:26][N:25]=3)=[CH:14][CH:13]=2)[C:9](=[O:48])[C:8]([CH2:49][CH3:50])=[C:7]([CH3:51])[N:6]=1)[CH2:2][CH2:3][CH3:4]>C(O)(=O)C.O.[Cl-].[Na+].O>[CH2:1]([C:5]1[N:10]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]3[NH:28][N:27]=[N:26][N:25]=3)=[CH:16][CH:17]=2)[C:9](=[O:48])[C:8]([CH2:49][CH3:50])=[C:7]([CH3:51])[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(C)c(CC)c(=O)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CCCCc1nc(C)c(CC)c(=O)n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1

Procedure:
A solution of 2-n-butyl-3-[(2'-(N-triphenylmethyl-tetrazol-5-yl)-biphen-4-yl)-methyl]-5-ethyl-6-methylpyrimidin-4(3H)-one (from Example 5) in 4 mL acetic acid and 2 mL water was stirred at room temperature for 6 hours. The reaction mixture was diluted with brine and extracted three times with ether. The combined organic material was washed with brine, was dried over MgSO4, was stripped of solvent in vacuo, and then was MPLC'd in 1 acetic acid/39 hexane/60 ethyl acetate to give the title compound as a white foam. 1H NMR (300 MHz, CDCl3) δ7.87 (m, 1H), 7.58 (m, 1H), 7.49 (m, 1H), 7.40 (m, 1H), 7.02 (4 line m, 4H), 5.19 (br s, 2H), 2.57 (3 line m, 2H), 2.42 (4 line m, 2H), 2.24 (s, 3H), 1.63 (m, 2H), 1.34 (m, 2H), 0.96 (3 line m, 3H), 0.88 (3 line m, 3H); IR (CHCl3) 3420 (br), 3020, 1645, 1530, 1120 cm-1 ; FABMS: 429 (M+1).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:11]=[C:10]2[C:6]([N:7]=[CH:8][N:9]2[C@H:12]2[C@H:16]([OH:17])[C@H:15]([OH:18])[C@@H:14]([CH2:19][O:20][CH3:21])[O:13]2)=[C:5]([NH:22][CH2:23][CH:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[N:4]=1.[CH3:37][CH:38]([CH3:44])[CH2:39][S:40](Cl)(=[O:42])=[O:41].C(N(CC)CC)C>O1CCCC1>[OH:17][C@@H:16]1[C@H:15]([OH:18])[C@@H:14]([CH2:19][O:20][CH3:21])[O:13][C@H:12]1[N:9]1[CH:8]=[N:7][C:6]2[C:10]1=[N:11][C:3]([CH2:2][NH:1][S:40]([CH2:39][CH:38]([CH3:44])[CH3:37])(=[O:42])=[O:41])=[N:4][C:5]=2[NH:22][CH2:23][CH:24]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: CC(C)CS(=O)(=O)Cl
Reactant: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CN)nc32)[C@H](O)[C@@H]1O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC[C@H]1O[C@@H](n2cnc3c(NCC(c4ccccc4)c4ccccc4)nc(CNS(=O)(=O)CC(C)C)nc32)[C@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 18 h
Yield: 59.9 %

Procedure:
(2R,3R,4S,5R)-2-{2-(Aminomethyl)-6-[(2,2-diphenylethyl)amino]-9H-purin-9-yl}-5-(methoxymethyl)tetrahydro-3,4-furandiol (example 1) (300 mg, 0.61 mmol) was dissolved in dry tetrahydrofuran (20 ml) (using gentle heating), a solution of 2-methyl-1-propanesulphonyl chloride (50 mg, 0.32 mmol) in dry tetrahydrofuran (2.5 ml) added and the mixture stirred at room temperature for 18 hr under a nitrogen atmosphere. A solution of triethylamine (100 mg, 0.98 mmol) and 2-methyl-1-propanesulphonyl chloride (50 mg, 0.32 mmol) in dry tetrahydrofuran (5 ml) was added and the resulting mixture stirred for a further 5 hr. The solvent was then removed under reduced pressure and the residue purified by column chromatography on silica gel eluting with a solvent system of dichloromethane:methanol (97:3), to give the product as a foam (117 mg). MS: 611 (MH+).
Reaction SMILES: [CH2:1]([N:8]([CH2:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[Br:24])[C:18]([OH:20])=O)[C:9]([CH:11]1[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25]([NH2:29])([CH3:28])([CH3:27])[CH3:26]>>[CH2:1]([N:8]([CH2:14][C:15]1[CH:16]=[C:17]([CH:21]=[CH:22][C:23]=1[Br:24])[C:18]([NH:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:20])[C:9]([CH:11]1[CH2:12][CH2:13]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1ccc(Br)c(CN(Cc2ccccc2)C(=O)C2CC2)c1
Reactant: CC(C)(C)N
Product: CC(C)(C)NC(=O)c1ccc(Br)c(CN(Cc2ccccc2)C(=O)C2CC2)c1

Procedure:
3-[(N-Benzyl-N-cyclopropanecarbonyl-amino)-methyl]-4-bromo-benzoic acid and tert-butylamine were reacted as described in Example 5, Step 6 to provide 3-[(N-benzyl-N-cyclopropanecarbonyl-amino)-methyl]-4-bromo-N-tert-butyl-benzamide
Reaction SMILES: C(S(C[C@@H](CC1C=CC=CC=1)C(N[C@@H](CC1N=CNC=1)C(N[C@@H:17]([CH2:25][CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)[C@@H:18](O)[C@@H:19]([OH:23])[CH:20]([CH3:22])[CH3:21])=O)=O)(=O)=O)(C)(C)C.[C:45]1(=[O:51])[O:50][C:48](=[O:49])[CH2:47][CH2:46]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(OCC)(=O)C>[C:45]([O:23][CH:19]([CH:20]([CH3:21])[CH3:22])[CH2:18][CH2:17][CH2:25][CH:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1)(=[O:51])[CH2:46][CH2:47][C:48]([OH:50])=[O:49]
Reactant: CC(C)[C@H](O)[C@H](O)[C@H](CC1CCCCC1)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)CS(=O)(=O)C(C)(C)C
Reactant: O=C1CCC(=O)O1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)C(CCCC1CCCCC1)OC(=O)CCC(=O)O

Procedure:
100 mg of (S)-α-[(S)-α[(t-butylsulphonyl)methyl]-hydrocinnamamido]-N-[(1S,2R,3S)-1-(cyclohexylmethyl)-2,3-dihydroxy-4-methylpentyl]imidazole-4-propionamide, 200 mg of succinic anhydride and 200 mg of sodium carbonate in 10 ml of dimethylformamide are stirred at 50° overnight. Thereafter, the reaction mixture is taken up in ethyl acetate and the organic phase is washed with saturated ammonium chloride solution and water, dried and evaporated. Chromatography of the resiude on 20 g of silica gel with a 90:10:1:0.5 mixture of methylene chloride, methanol, water and acetic acid yields (1S,2R,3S)-3-[(S)-α-[(t-butylsulphonyl)methyl]-hydrocinnamamido]imidazole-4-propionamido]-4-cyclohexyl-1-isopropylbutyl hydrogen succinate as a foam, MS: 733 (M+H)+, and (1R,2S)-1-[(S)-1-[(S)-α-[(t-butylsulphonyl)methyl]hydrocinnamamido]imidazole-4-propionamide]-2-cyclohexylethyl]-2-isopropylethylene bis(hydrogen succinate) in the form of a foam, MS: 833 (M+H)+.
Reaction SMILES: C(O[C:6](=O)[N:7]([C@@H:9]([C:21](=[O:40])[N:22]([C@@H:24]([CH2:32][O:33][CH2:34][C:35](=[O:39])[N:36]([CH3:38])[CH3:37])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH3:23])[CH2:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=1)C)(C)(C)C.C(OC([NH:49][CH2:50][C:51]1[CH:52]=[C:53]([CH:57]=[CH:58][CH:59]=1)[C:54]([OH:56])=O)=O)(C)(C)C.Cl.C(N=C=NCCCN(C)C)C>ClCCl.FC(F)(F)C(O)=O>[NH2:49][CH2:50][C:51]1[CH:52]=[C:53]([CH:57]=[CH:58][CH:59]=1)[C:54]([N:7]([C@@H:9]([C:21](=[O:40])[N:22]([C@@H:24]([CH2:32][O:33][CH2:34][C:35](=[O:39])[N:36]([CH3:37])[CH3:38])[CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[CH3:23])[CH2:10][C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=1)[CH3:6])=[O:56]
Reactant: CN(C)C(=O)COC[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](Cc1ccc2ccccc2c1)N(C)C(=O)OC(C)(C)C
Reactant: CC(C)(C)OC(=O)NCc1cccc(C(=O)O)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CN(C)C(=O)COC[C@@H](Cc1ccccc1)N(C)C(=O)[C@@H](Cc1ccc2ccccc2c1)N(C)C(=O)c1cccc(CN)c1
Reaction time: 0.17 h

Procedure:
Half of the crude N-((1R)-1-{N-[(1R)-1-(((dimethylcarbamoyl)methoxy)methyl)-2-phenylethyl]-N-methylcarbamoyl}-2-{2-naphthyl}ethyl)-N-methylcarbamic acid tert-butylester (132 mg, 0.23 mmol) was dissolved in a mixture of dichloromethane and trifluoroacetic acid 1:1 (2 ml) and stirred for 10 min. The mixture was concentrated by a stream of nitrogen and the resulting oil was redissolved in 1 ml 1N hydrochloric acid, diluted with water to a volume of 50 ml and lyophilized. This lyophilized product was dissolved in dichloromethane (5 ml) and diisopropylethyl amine (171 μl) was added. To this mixture was added a solution in dichloromethane (5 ml) of 3-tert-butyloxycarbonylaminomethylbenzoic acid (503 mg, 2.0 mmol) which immediately before had been converted to the symmetrical anhydride by stirring with N-ethyl-N'-(3-dimethylaminopropyl)-carbodiimide hydrochloride (191.6 mg, 1.0 mmol) for 15 min. The reaction mixture was then concentrated to an oil and redissolved in ethyl acetate (25 ml). This mixture was extracted sequentially with 5% aqueous sodium hydrogencarbonate (50 ml), 5% aqueous potassium hydrogen-sulfate (50 ml) and water (50 ml) and the organic phase was dried (sodium sulfate) and concentrated by a stream of nitrogen to dryness. This product was dissolved in a mixture of dichloromethane and trifluoroacetic acid 1:1 (4 ml). After 10 min the mixture was concentrated by a stream of nitrogen and the resulting oil was redissolved in 5 ml 70% acetonitrile/0.1% trifluoroacetic acid and diluted with water to a volume of 50 ml. The crude product of the title compound was then purified by semipreparative HPLC in four runs on a 25 mm×250 mm column packed with 7μ C-18 silica which was preequilibrated with 29% acetonitrile in 0.05M ammonium sulfate, which was adjusted to pH 2.5 with 4M sulfuric acid.
Reaction SMILES: [CH3:1][CH:2]1[CH2:9][C@H:8]2[C@H:4]([CH2:5][NH:6][C@@H:7]2[CH2:10][NH:11][C:12]([C:14]2[N:21]3[C:17]([S:18][CH:19]=[CH:20]3)=[N:16][C:15]=2[CH3:22])=[O:13])[CH2:3]1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[S:35][C:34]([CH3:36])=[N:33][C:32]=2[C:37](O)=[O:38])=[CH:27][CH:26]=1>>[CH3:23][O:24][C:25]1[CH:26]=[CH:27][C:28]([C:31]2[S:35][C:34]([CH3:36])=[N:33][C:32]=2[C:37]([N:6]2[CH2:5][C@H:4]3[C@H:8]([CH2:9][CH:2]([CH3:1])[CH2:3]3)[C@H:7]2[CH2:10][NH:11][C:12]([C:14]2[N:21]3[C:17]([S:18][CH:19]=[CH:20]3)=[N:16][C:15]=2[CH3:22])=[O:13])=[O:38])=[CH:29][CH:30]=1
Reactant: Cc1nc2sccn2c1C(=O)NC[C@H]1NC[C@@H]2CC(C)C[C@@H]21
Reactant: COc1ccc(-c2sc(C)nc2C(=O)O)cc1
Product: COc1ccc(-c2sc(C)nc2C(=O)N2C[C@@H]3CC(C)C[C@@H]3[C@H]2CNC(=O)c2c(C)nc3sccn23)cc1

Procedure:
prepared by reaction of 6-methyl-imidazo[2,1-b]thiazole-5-carboxylic acid-[(1S,2S,5R)-7-methyl-3-aza-bicyclo[3.3.0]oct-2-ylmethyl]-amide with 5-(4-methoxy-phenyl)-2-methyl-thiazole-4-carboxylic acid.
Reaction SMILES: C(O)(=O)C.[CH2:5]([N:12]1[CH2:18][C:16](=[O:17])[NH:15][C:13]1=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.BrBr.[CH2:21]([OH:24])[CH2:22][OH:23]>O>[CH2:5]([N:12]1[CH:18]([O:23][CH2:22][CH2:21][OH:24])[C:16](=[O:17])[NH:15][C:13]1=[O:14])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: O=C1CN(Cc2ccccc2)C(=O)N1
Reactant: OCCO
Agent: BrBr
Solvent: CC(=O)O
Solvent: O
Product: O=C1NC(=O)N(Cc2ccccc2)C1OCCO
Temperature: 80 °C
Yield: 69.3 %

Procedure:
500 ml of acetic acid was added to 57 g of 1-benzylhydantoin and, while maintaining at 80° C. with stirring, 50.3 g of bromine was dropwise added thereto. After completion of the dropwise addition, the solution was further stirred for 2 hours. The reaction solution was then cooled and, while cooling with ice, 56 g of ethylene glycol was added thereto. After stirring for 30 minutes, the solution was further stirred for 3 hours at room temperature. One liter of water was added to the reaction solution, followed by extraction with 500 ml of ethyl acetate. The extract was further washed twice with 500 ml of water. The thus obtained ethyl acetate solution was dried with sodium sulfate, concentrated, and purified by silica gel chromatography to obtain 52 g of 1-benzyl-5-(2-hydroxyethoxy)hydantoin. (Yield: 74%)
Reaction SMILES: [OH-].[Na+:2].[C:3]([OH:13])(=[O:12])[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>O>[C:3]([O-:13])(=[O:12])[CH:4]=[CH:5][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1.[Na+:2]
Reactant: O=C(O)C=Cc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C([O-])C=Cc1ccccc1

Procedure:
In 300 ml of purified water, 1.64 g of sodium hydroxide was dissolved. In the resultant aqueous solution, 6.06 g of cinnamic acid (purity 99.9%, conjugate number 4) was throughly dissolved while under stirring, to produce a sodium cinnamate aqueous solution. To this aqueous solution, a europium chloride aqueous solution obtained in advance by thoroughly dissolving 5.0 g of europium chloride (EuCl3.6H2O; purity 99.99%) in 100 ml of purified water was gradually added at room temperature while under stirring. During the reaction, the pH value of the reaction solution was adjusted to a varying value indicated in Table 2. Then, it was subjected to continued thorough stirring and thereafter subjected to filtration. Then, the separated reaction product was thoroughly washed with 500 ml of purified water and dried in vacuo at 80° to 100° C. for 20 to 24 hours. Consequently, the products indicated in Table 2 were obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[C:8]([O:12][CH3:13])[C:9]=1[O:10][CH3:11])[NH2:6].[Cl:14][CH2:15][C:16](Cl)=[O:17]>C1(C)C=CC=CC=1>[Cl:14][CH2:15][C:16]([NH:6][C:5]1[CH:7]=[C:8]([O:12][CH3:13])[C:9]([O:10][CH3:11])=[C:3]([O:2][CH3:1])[CH:4]=1)=[O:17]
Reactant: COc1cc(N)cc(OC)c1OC
Reactant: O=C(Cl)CCl
Solvent: Cc1ccccc1
Product: COc1cc(NC(=O)CCl)cc(OC)c1OC
Temperature: 25 °C
Yield: 91.2 %

Procedure:
3,4,5-Trimethoxyaniline (Aldrich, 4.06 g, 22.2 mmol) and chloroacetyl chloride (2.60 mL, 32.7 mmol) in toluene (50 mL) were heated at 100° C. for 24 hours. The mixture was allowed to cool to room temperature and the volatiles were removed under reduced pressure. The residue was taken up in toluene and concentrated (3×) to remove traces of starting acid chloride and placed under high vacuum to provide 5.26 g (91%) of the title compound as a light brown solid. 1H NMR (500 MHz, DMSO-d6) δ 3.62 (s, 3H), 3.74 (s, 6H), 4.21 (s, 2H), 6.96 (s, 2H), 10.19 (br s, 1H); MS (DCI/NH3) m/e 260 (M+H)+.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:14]=[C:13]([O:15][CH2:16][C:17]([N:19]2[CH2:23][CH2:22][C:21]([F:25])([F:24])[CH2:20]2)=[O:18])[C:12]2[C:7](=[CH:8][C:9]([CH3:26])=[CH:10][CH:11]=2)[N:6]=1)=[O:4].[OH-].[Na+]>C1COCC1>[F:25][C:21]1([F:24])[CH2:22][CH2:23][N:19]([C:17](=[O:18])[CH2:16][O:15][C:13]2[C:12]3[C:7](=[CH:8][C:9]([CH3:26])=[CH:10][CH:11]=3)[N:6]=[C:5]([C:3]([OH:4])=[O:2])[CH:14]=2)[CH2:20]1
Reactant: COC(=O)c1cc(OCC(=O)N2CCC(F)(F)C2)c2ccc(C)cc2n1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1ccc2c(OCC(=O)N3CCC(F)(F)C3)cc(C(=O)O)nc2c1
Reaction time: 2 h

Procedure:
To a solution of 815 mg 4-[2-(3,3-Difluoro-pyrrolidin-1-yl)-2-oxo-ethoxy]-7-methyl-quinoline-2-carboxylic acid methyl ester in 8 ml THF were added 2.2 ml aqueous NaOH (1 M) at 0° C. After 2 h the mixture was brought to pH 4 by using Amberlite IR-120 ion exchange resin. The reaction mixture was filtered and concentrated and the crude product obtained used in the next step without further purification. Yield: 658 mg.
Reaction SMILES: CCOCC.[H-].[H-].[H-].[H-].[Li+].[Al+3].[Cl:12][C:13]1[CH:14]=[C:15]([CH:20]([CH2:26][N+:27]([O-])=O)[CH2:21][C:22](OC)=[O:23])[CH:16]=[CH:17][C:18]=1[Cl:19]>O1CCCC1>[NH2:27][CH2:26][CH:20]([C:15]1[CH:16]=[CH:17][C:18]([Cl:19])=[C:13]([Cl:12])[CH:14]=1)[CH2:21][CH2:22][OH:23]
Reactant: COC(=O)CC(C[N+](=O)[O-])c1ccc(Cl)c(Cl)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: NCC(CCO)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 75.2 %

Procedure:
To a 1M Et2O solution of LiAlH4 (200 mL, 200 mmol) at 0° C., slowly add the product of Step 2 (14.35 g, 49.1 mmol) dissolved in tetrahydrofuran (THF) (100 mL). Allow the reaction mixture to warm to room temperature and stir for 45 min. After recooling to 0° C., quench the excess LiAlH4 by the careful addition of aqueous saturated Na2SO4 (20 mL). Dry the solution with Na2SO4 and filter. Wash the lithium salts with Et2O (3×300 mL). Concentrate the combined filtrates to give 8.65 g of 4-amino-3-(3,4-dichlorophenyl)-butanol as a white solid (36.9 mmol, 75%).
Reaction SMILES: [CH2:1]([O:8][CH:9]([CH2:12][OH:13])[CH2:10][OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[CH:17](OCC)[CH2:18][Br:19])C>>[CH2:1]([O:8][CH:9]1[CH2:10][O:11][CH:17]([CH2:18][Br:19])[O:13][CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(CBr)OCC
Reactant: OCC(CO)OCc1ccccc1
Product: BrCC1OCC(OCc2ccccc2)CO1

Procedure:
By the method of Example 38, 2-benzyloxy-1,3-propanediol was reacted with bromoacetaldehyde diethyl acetal to yield 5-benzyloxy-2-bromomethyl-1,3-dioxane; b.p. 130°-133° C/10-4 mm Hg; nD25 1.5395. The nmr spectrum was consistent with the assigned structure and indicated the cis-isomer content was 30 ± 5%, the remainder being trans.
Reaction SMILES: C([Li])CCC.[CH2:6]([C@H:13]1[CH2:17][O:16][C:15](=[O:18])[NH:14]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:19](Cl)(=[O:29])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>C1COCC1>[O:29]=[C:19]([N:14]1[C@@H:13]([CH2:6][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:17][O:16][C:15]1=[O:18])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCCCCC(=O)Cl
Reactant: O=C1N[C@@H](Cc2ccccc2)CO1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCCCCCCCC(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
n-Butyl lithium (160 mL, 398 mmol, 2.5M in hexanes) is added to a solution of (S)-4-benzyl-2-oxazolidinone 51 (64 g, 362 mmol) in THF (750 mL) at -78° C. under argon and stirred for 15 min. Decanoyl chloride 59 (69 g, 362 mmol) is added to the solution dropwise and stirred for 40 min, then warmed to 0° C. for 2 hours. The reaction is quenched with NH4Cl and extracted with EtOAc. The organic layer is washed with 1N HCl, aqueous NaHCO3, aqueous NaCl, and dried over MgSO4. The crude product is recrystallized from hexane to give 60.
Reaction SMILES: [C:1]1([CH:7]2[NH:10][C:9](=[O:11])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:12]([Si:16](Cl)([CH3:18])[CH3:17])([CH3:15])([CH3:14])[CH3:13].C(N(CC)CC)C>CN(C=O)C>[C:1]1([CH:7]2[N:10]([Si:16]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:18])[CH3:17])[C:9](=[O:11])[CH2:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: O=C1CC(c2ccccc2)N1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)N1C(=O)CC1c1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 99.1 %

Procedure:
4-Phenylazetidin-2-one (10.4 gm, 71.0 mmole) (Graf, Chem. Ber, 111 (1963); Durst et al. J. Org. Chem., 35, 2043 (1970)) was dissolved in DMF (200 ml) and was treated with tert.-butyldimethylsilyl chloride (12.8 gm, 85 mmol) and triethylamine (11.8 ml, 85 mmol). The mixture was stirred at room temperature for 16 hrs. and taken up in either (500 ml). The ethereal solution was washed with 1N hydrochloric acid (1×100 ml), water (2×50 ml) and brine (1×50 ml). After the solution was dried (anhyd. magnesium sulfate) and evaporated, the residue was flash chromatographed on SiO2 -gel column. Elution with 15% ethyl acetate in hexane afforded 4-phenyl-1-(tert.-butyldimethylsilyl)azetidin-2-one (18.4 gm, 99%) as an oil which solidified on standing.
Reaction SMILES: [Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][CH:7]2[C:11]([CH2:13][N:14]3[CH:18]=[N:17][CH:16]=[N:15]3)([OH:12])[C:10]([CH2:21][OH:22])([CH2:19][OH:20])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[S:32](Cl)([CH3:35])(=[O:34])=[O:33]>COCCOC>[CH3:35][S:32]([O:22][CH2:21][C:10]1([CH2:19][O:20][S:32]([CH3:35])(=[O:34])=[O:33])[CH2:9][CH2:8][CH:7]([CH2:6][C:5]2[CH:23]=[CH:24][C:2]([Cl:1])=[CH:3][CH:4]=2)[C:11]1([OH:12])[CH2:13][N:14]1[CH:18]=[N:17][CH:16]=[N:15]1)(=[O:34])=[O:33]
Reactant: CS(=O)(=O)Cl
Reactant: OCC1(CO)CCC(Cc2ccc(Cl)cc2)C1(O)Cn1cncn1
Solvent: CCN(CC)CC
Solvent: COCCOC
Product: CS(=O)(=O)OCC1(COS(C)(=O)=O)CCC(Cc2ccc(Cl)cc2)C1(O)Cn1cncn1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
5-(4-chlorobenzyl)-2,2-bis(hydroxymethyl)-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol (0.50 g, 1.42 mmol) (Compound (4)) and triethyl amine (0.70 ml, 1.42×3.5 mmol) were dissolved in DME (15 ml). After adding mesyl chloride (0.30 ml, 1.42×2.7 mmol) under ice-cooling, the solution was removed from the ice bath and stirred for 5 hours at room temperature. After the stirring was complete, 1N aqueous solution of hydrochloric acid was added and then extracted using ethyl acetate. After washing the organic layer using a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, the organic layer was dried using anhydrous sodium sulfate and then concentrated. The concentrate was refined using a silica gel column to obtain white, viscous Compound (3).
Reaction SMILES: [C:1]([OH:14])(=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]([OH:12])=[O:11].[CH3:15][C:16]([CH2:21][CH3:22])([CH2:19]O)[CH2:17]O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)(Cl)Cl>[C:1]1(=[O:14])[O:13][CH2:17][C:16]([CH3:19])([CH2:21][CH3:22])[CH2:15][O:12][C:10](=[O:11])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CCC(C)(CO)CO
Reactant: O=C(O)CCCCCCCCC(=O)O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClC(Cl)Cl
Product: CCC1(C)COC(=O)CCCCCCCCC(=O)OC1
Temperature: 25 °C

Procedure:
Amorphous poly (2-methyl-2 -ethyl-1,3-propylene sebacate) was prepared by reacting sebacic acid and a 10 mole % excess of 2-methyl-2-ethyl-1,3-propylene glycol in the presence of 0.5 weight % p-toluenesulfonic acid in the same manner as in Example 1. On cooling to room temperature after the polymerization, the poly (MEPS) remained as a clear, tacky fluid. Analysis indicates it has an acid number of 2.40, an hydroxyl number of 19.4, an Mn of 5150 g/mole, an MWD of 1.87 by GPC in chloroform, and a glass transition temperature of about -61°C.
Reaction SMILES: [F:1][C:2]1[N:7]=[C:6](F)[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=1.[CH:13]1([NH2:16])[CH2:15][CH2:14]1>>[CH:13]1([NH:16][C:6]2[CH:5]=[C:4]([C:9]([F:12])([F:11])[F:10])[N:3]=[C:2]([F:1])[N:7]=2)[CH2:15][CH2:14]1
Reactant: NC1CC1
Reactant: Fc1cc(C(F)(F)F)nc(F)n1
Product: Fc1nc(NC2CC2)cc(C(F)(F)F)n1

Procedure:
If, for example, 2,4-difluoro-6-trifluoromethylpyrimidine and cyclopropylamine are used as starting materials and the 4-cyclopropylamino-2-fluoro-6-trifluoromethylpyrimidine thereby formed is reacted with 3-methoxypropylamine, then the course of the reaction can be summarized by the following reaction scheme: ##STR7##