Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3]1C=CC=[CH:5][C:4]=1[C:9]([CH:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)O)=O.C1(C2[S:30][CH2:29][CH2:28][CH2:27][S:26]2)C=CC=CC=1.COC1C=C(C=C(OC)C=1)C(O)C(=O)C1C=CC=CC=1.C(O)(=O)C=C.COC1C=C(C=C(OC)C=1)C(O)C(=O)C1C=CC=CC=1.C(Cl)(=O)C=C.C1C2C(=CC=CC=2)C=CC=1C=O.S1C=CCS1.C(S)CCS.Cl>C(Cl)(Cl)Cl>[CH:5]1[C:14]2[C:13](=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:11]=[CH:9][C:4]=1[CH:3]1[S:30][CH2:29][CH2:28][CH2:27][S:26]1
Reactant: c1ccc(C2SCCCS2)cc1
Reactant: COc1ccccc1C(=O)C(O)c1ccccc1
Agent: C1=CSSC1
Agent: C=CC(=O)Cl
Agent: C=CC(=O)O
Solvent: ClC(Cl)Cl
Product: c1ccc2cc(C3SCCCS3)ccc2c1

Procedure:
The special characteristic of the polymeric compound of the invention is the methoxybenzoin (3'-; 3',4'-; or 3',5'-) group of the polymer. The compound is photosensitive per se without the presence of other photosensitive groups. The precursors of a polymeric compound, e.g., poly(3',5'-dimethoxybenzoinacrylate), are set forth in Example 1 below. For example, 2-phenyl-1,3-dithiane is prepared as described by Seebach et al., J. Org. Chem. 31, 4303 (1966). This compound is then used to prepare 2-[1-hydroxy-1-(3,5-dimethoxyphenyl)]methyl-2-phenyl-1,3-dithiane by the general procedure described by Seebach et al., J. Org. Chem. 40, 231 (1975). 3',5'-dimethoxybenzoin is subsequently prepared by thioketal hydrolysis according to the general procedure described by Naraska et al., Bull. Chem. Soc. Japan (Tokyo), 45, 3724 (1972). This compound is esterified to 3',5'-dimethoxybenzoin acrylate by known esterification procedures using acryloyl chloride and then is polymerized in a known way to form a polymer of the invention. An alternative procedure for preparing a substituted benzoin acrylate monomer illustrated in Example 3 is as follows: an aldehyde, e.g., β-naphthaldehyde and a dithiol, e.g., 1,3-propanedithiol, are reacted in a solvent, e.g., chloroform saturated with HCl, to form 2-β-naphthyl-1,3-dithiane. To the isolated product in anhydrous tetrahydrofuran is added n-butyllithium/hexane at dry ice/acetone temperature. Subsequently 3,5-dimethoxybenzaldehyde in the same solvent is added and stirred followed 30 minutes later by acryloyl chloride in solvent to form 3,4-benzo-3',5'-dimethoxybenzoin acrylate thioketal. Hydrolysis of the thioketal as described above produces 3,4-benzo-3',5'-dimethoxybenzoin acrylate. It is recognized that analogues of the above compounds can be prepared by the foregoing procedures. The proportions of the various repeating units in the final copolymer can be controlled by controlling the quantities of reactants present during copolymerization.
Reaction SMILES: [CH2:1]([O:13][C:14]1[CH:18]=[CH:17][S:16][C:15]=1[C:19]1[S:20][CH:21]=[CH:22][C:23]=1[O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[Li]CCCC.[CH3:42][Sn:43](Cl)([CH3:45])[CH3:44]>C1COCC1.C(OCC)(=O)C>[CH3:42][Sn:43]([CH3:45])([CH3:44])[C:17]1[S:16][C:15]([C:19]2[S:20][C:21]([Sn:43]([CH3:45])([CH3:44])[CH3:42])=[CH:22][C:23]=2[O:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[C:14]([O:13][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH:18]=1
Reactant: CCCCCCCCCCCCOc1ccsc1-c1sccc1OCCCCCCCCCCCC
Reactant: C[Sn](C)(C)Cl
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCCCCCCCCCOc1cc([Sn](C)(C)C)sc1-c1sc([Sn](C)(C)C)cc1OCCCCCCCCCCCC
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 81.5 %

Procedure:
A solution of 2.9 g (5.42 mmol) of 3,3′-didodecyloxy-2,2′-bithiophene (Org. Lett. 2008, 10, 5333) in 150 mL of THF was cooled to −78° C. The resulting suspension was treated dropwise with 5.2 mL (13.0 mmol) of n-BuLi (2.5 M in hexanes) and stirred for an additional 45 minutes. The dry ice bath was then removed and the mixture was stirred at ambient temperature for 1.25 hours. The suspension was cooled to −78° C. and treated with a solution of 3.02 g (15.2 mmol) of trimethyltin chloride in 15 mL of THF. The mixture was stirred for 90 minutes at ambient temperature. The mixture was diluted with 100 mL of ethyl acetate and washed successively with 50 mL of water and 50 mL of brine. The separated organic layer was dried over K2CO3, filtered, and concentrated in vacuo. The resulting solid was recrystallized from cold pentane to give 3.8 g (81% yield) of 5,5′-bis(trimethylstannyl)-3,3′-bis(dodecyloxy)2,2′-bithiophene as light tan needles. m.p. 66-67° C. 1H NMR (500 MHz) δ 6.88 (s, 2H), 4.11 (t, 4H, J=6.4 Hz), 1.84 (m, 4H), 1.55-1.30 (m, 36H), 0.88 (m, 6H), 0.36 (s, 18H).
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]1[CH2:11][NH:10][CH2:9][CH2:8][N:7]1[S:12]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]#[C:24][CH3:25])=[CH:17][CH:16]=1)(=[O:14])=[O:13])=[O:5])[CH3:2].C(N(CC)CC)C.[C:33](Cl)(=[O:35])[CH3:34]>ClCCl.CN(C1C=CN=CC=1)C.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([CH:6]1[CH2:11][N:10]([C:33](=[O:35])[CH3:34])[CH2:9][CH2:8][N:7]1[S:12]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]#[C:24][CH3:25])=[CH:17][CH:16]=1)(=[O:13])=[O:14])=[O:5])[CH3:2]
Reactant: CC#CCOc1ccc(S(=O)(=O)N2CCNCC2C(=O)OCC)cc1
Reactant: CC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CC#CCOc1ccc(S(=O)(=O)N2CCN(C(C)=O)CC2C(=O)OCC)cc1
Reaction time: 13 h
Yield: 68.3 %

Procedure:
To a solution of 0.170 g (0.466 mmol) of 1-(4-but-2-ynyloxy-benzenesulfonyl)-piperazine-2-carboxylic acid ethyl ester in 10 mL of dichloromethane cooled at 0° was added 0.2 mL of triethylamine, 0.05 g of DMAP and 0.3 mL (0.93 mmol) of acetyl chloride. After stirring for 13 h the mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was chromatographed on silica gel eluting with ethyl acetate/hexanes (2:1) to provide 0.13 g (68%) of 4-acetyl-1-(4-but-2-ynyloxy-benzenesulfonyl)-piperazine-2-carboxylic acid ethyl ester as a brown oil. Electrospray Mass Spec: 409.3 (M+H)+
Reaction SMILES: [F:1][C:2]1[CH:15]=[CH:14][C:13]2[N:12]([S:16]([C:19]3[CH:24]=[CH:23][C:22]([O:25]C)=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH:11]([CH3:27])[C:10]3[C:5](=[CH:6][C:7]([F:28])=[CH:8][CH:9]=3)[C:4]=2[CH:3]=1.C1CCCCC=1.B(Br)(Br)Br>ClCCl>[F:1][C:2]1[CH:15]=[CH:14][C:13]2[N:12]([S:16]([C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH:11]([CH3:27])[C:10]3[C:5](=[CH:6][C:7]([F:28])=[CH:8][CH:9]=3)[C:4]=2[CH:3]=1
Reactant: COc1ccc(S(=O)(=O)N2c3ccc(F)cc3-c3cc(F)ccc3C2C)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Solvent: C1=CCCCC1
Product: CC1c2ccc(F)cc2-c2cc(F)ccc2N1S(=O)(=O)c1ccc(O)cc1
Yield: 81.6 %

Procedure:
The title compound was prepared from 2,9-difluoro-5-[(4-methoxyphenyl)sulfonyl]-6-methyl-5,6-dihydrophenanthridine (150 mg, 0.37 mmol), cyclohexene (757 μL, 7.5 mmol), and 1.0 M solution of boron tribromide in dichloromethane (2.24 mL) according to the procedure and in the same manner as described in Example 105, step e. The volatile components were removed in vacuo and the crude residue was purified on a Biotage® 40 Mi column of prepacked silica gel (90 g), eluting with a gradient of 5%-50% methyl tert-butyl ether in hexane, to afford the desired compound (117 mg, 81%) as a white solid, m.p. 194-196° C.;
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:14]([CH3:16])[CH3:15])=[CH:4][C:5]([O:11][CH2:12][CH3:13])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[NH2:17][CH:18]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:19]1>>[CH2:23]([N:20]1[CH2:21][CH2:22][CH:18]([NH:17][C:7](=[O:9])[C:6]2[CH:10]=[C:2]([Cl:1])[C:3]([N:14]([CH3:16])[CH3:15])=[CH:4][C:5]=2[O:11][CH2:12][CH3:13])[CH2:19]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CCOc1cc(N(C)C)c(Cl)cc1C(=O)O
Reactant: NC1CCN(Cc2ccccc2)C1
Product: CCOc1cc(N(C)C)c(Cl)cc1C(=O)NC1CCN(Cc2ccccc2)C1

Procedure:
Following the procedure set forth in general method A supra using 1.22 g. of 5-chloro-4-dimethylamino-2-ethoxybenzoic acid and 0.97 g. of 3-amino-1-benzylpyrrolidine, 1.7 g. of N-(1-benzyl-3-pyrrolidinyl)-5-chloro-4-dimethylamino-2-ethoxybenzamide was obtained.
Reaction SMILES: [CH2:1]([NH:3][C:4]([CH:6]1[CH2:10][CH:9]([N:11]2[C:15]3[N:16]=[C:17]([S:30][CH2:31][CH2:32][CH3:33])[N:18]=[C:19]([NH:20][CH:21]4[CH2:23][CH:22]4[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[C:14]=3[N:13]=[N:12]2)[CH:8]([OH:34])[CH:7]1[OH:35])=[O:5])[CH3:2].[Cl:36][C:37]1[CH:38]=C([CH:42]=[CH:43][CH:44]=1)CN>>[Cl:36][C:37]1[CH:38]=[C:2]([CH2:1][NH:3][C:4]([CH:6]2[CH2:10][CH:9]([N:11]3[C:15]4[N:16]=[C:17]([S:30][CH2:31][CH2:32][CH3:33])[N:18]=[C:19]([NH:20][CH:21]5[CH2:23][CH:22]5[C:24]5[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=5)[C:14]=4[N:13]=[N:12]3)[CH:8]([OH:34])[CH:7]2[OH:35])=[O:5])[CH:42]=[CH:43][CH:44]=1
Reactant: NCc1cccc(Cl)c1
Reactant: CCCSc1nc(NC2CC2c2ccccc2)c2nnn(C3CC(C(=O)NCC)C(O)C3O)c2n1
Product: CCCSc1nc(NC2CC2c2ccccc2)c2nnn(C3CC(C(=O)NCc4cccc(Cl)c4)C(O)C3O)c2n1

Procedure:
The subtitle compound was prepared according to the method of example 39, step a) using the product of example 1, step c) and 3-chlorobenzylamine.
Reaction SMILES: ClC1C=CSC=1C([N:9]([C:11]([N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:12])[NH2:10])=O.[Cl:19][C:20]1[CH:24]=[CH:23][S:22][C:21]=1[C:25](NN)=O.CCN(CC)CC.N1(C(Cl)=O)CCCCC1>O.C1COCC1>[Cl:19][C:20]1[CH:24]=[CH:23][S:22][C:21]=1[C:25]1[O:12][C:11]([N:13]2[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]2)=[N:9][N:10]=1
Reactant: NN(C(=O)c1sccc1Cl)C(=O)N1CCCCC1
Reactant: NNC(=O)c1sccc1Cl
Agent: O=C(Cl)N1CCCCC1
Solvent: O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Clc1ccsc1-c1nnc(N2CCCCC2)o1
Reaction time: 18 h
Yield: 86 %

Procedure:
Piperidine-1-carboxylic acid N-(3-chlorothiophene-2-carbonyl)-hydrazide. A yellow solution of 3-chlorothiophene-2-carboxylic acid hydrazide (0.150 g, 0.852 mmol), THF (1.7 mL) and Et3N (0.12 mL, 0.852 mmol) was cooled to 0° C. and 1-piperidinecarbonyl chloride (0.106 mL, 0.852 mmol) was added dropwise. The yellow solution was equilibrated to room temperature and stirred for 18 h The reaction solution was diluted with water (20 mL) and then extracted with ethyl acetate (30 mL). The organic layer was washed with water (15 mL), brine (10 mL), dried over MgSO4, and then concentrated to yield 0.210 g (86%) of the title compound as a white solid. 1H NMR (CDCl3): 9.29 (d, 1H, J=5.2 Hz), 7.51-7.48 (m, 2H), 7.00 (d, 1H, J=5.2 Hz), 3.45-3.43 (m, 4H), 1.64-1.60 (m, 6H).
Reaction SMILES: [N+:1]([C:4]12[CH2:13][CH:8]3[CH2:9][CH:10]([CH2:12][C:6]([N+:14]([O-])=O)([CH2:7]3)[CH2:5]1)[CH2:11]2)([O-:3])=[O:2]>[Ni].[Pd]>[NH2:14][C:6]12[CH2:7][CH:8]3[CH2:9][CH:10]([CH2:11][C:4]([N+:1]([O-:3])=[O:2])([CH2:13]3)[CH2:5]1)[CH2:12]2
Reactant: O=[N+]([O-])C12CC3CC(C1)CC([N+](=O)[O-])(C3)C2
Agent: [Ni]
Agent: [Pd]
Product: NC12CC3CC(C1)CC([N+](=O)[O-])(C3)C2
Reaction time: 4 h
Yield: 80 %

Procedure:
The reaction was effected in the same manner as Example 65 except for using Raney nickel (5 mole % of Ni relative to a substrate) instead of 5% Pd-C and that reacting for 4 hours. The conversion of 1,3-dinitroadamantane was 99%, and 1-amino-3-nitroadamantane (yield 80%) was formed.
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[CH2:17][NH:16][CH2:15][CH2:14]3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.C=O.[BH-](OC(C)=O)(OC(C)=O)O[C:25](C)=O.[Na+].CC(O)=O.[OH-].[Na+]>CO>[Br:1][C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[CH2:17][N:16]([CH3:25])[CH2:15][CH2:14]3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1
Reactant: Cn1cc(Br)nc(Nc2ccc3c(c2)CCNC3)c1=O
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C=O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CC(=O)O
Product: CN1CCc2cc(Nc3nc(Br)cn(C)c3=O)ccc2C1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of 221a (2.75 g, 7.5 mmol), formaldehyde (37% in H2O, 30 mL, 375 mmol), NaBH(OAc)3 (4.75 g, 22.5 mmol), and AcOH (25 ml, 150 mmol) in methanol (125 ml) was stirred for 4 hours at room temperature. The mixture was then brought to basic condition with saturated NaOH solution and extracted with ethyl acetate. The organic layer was dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by column chromatography eluting with 4:1 ethyl acetate/methanol to give 221b. (0.9 g, 34.4%) LC/MS: m/z 350 (M+H)+
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8]/[N:9]=[CH:10]/[CH:11]=[C:12]2[C:17](=[O:18])[O:16]C(C)(C)[O:14][C:13]2=O)=[CH:4][CH:3]=1.C[O-].[Na+].Cl>CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]([C:17]([OH:16])=[O:18])=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:3]=1
Reactant: CC1(C)OC(=O)C(=C/C=N/Nc2ccc(F)cc2)C(=O)O1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: O=C(O)c1ccnn(-c2ccc(F)cc2)c1=O
Yield: 87.5 %

Procedure:
A mixture of (E)-5-(2-(2-(4-fluorophenyl)hydrazono)ethylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (0.60 g, 2.05 mmol) and NaOMe (0.133 g, 2.46 mmol) in MeOH (10 mL) was heated under reflux for 15 hours. The salt was treated with cold 1 N HCl solution, extracted with DCM, dried over MgSO4, and concentrated to afford 0.42 g (87%) of the desired product. 1H NMR (400 MHz, CDCl3) δ 13.57 (br s, 1H), 8.29 (m, 2H), 7.63 (m, 2H), 7.24 (m, 2H); 19F NMR (376 MHz, CDCl3) δ −110.7. LRMS (ESI pos) m/e 235.1 (M+1).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[F:12])[C:5](=[N:7][OH:8])[NH2:6].[N:13]1[CH:18]=[C:17]([C:19]([Cl:21])=[O:20])[CH:16]=[N:15][CH:14]=1.N1C=C(C(O)=O)C=NC=1.C(Cl)(=O)C(Cl)=O>>[F:1][C:2]1[CH:3]=[C:4]([C:5]2[N:6]=[C:19]([C:17]3[CH:18]=[N:13][CH:14]=[N:15][CH:16]=3)[O:8][N:7]=2)[CH:9]=[CH:10][C:11]=1[F:12].[N:13]1[CH:18]=[C:17]([C:19]([Cl:21])=[O:20])[CH:16]=[N:15][CH:14]=1
Reactant: NC(=NO)c1ccc(F)c(F)c1
Agent: O=C(Cl)C(=O)Cl
Agent: O=C(Cl)c1cncnc1
Agent: O=C(O)c1cncnc1
Product: Fc1ccc(-c2noc(-c3cncnc3)n2)cc1F

Procedure:
The titled compound was prepared according to the procedure of Method D using 3,4-difluoro-N′-hydroxybenzimidamide (Tyger) and pyrimidine-5-carbonyl chloride. The pyrimidine-5-carbonyl chloride was prepared by the reaction of pyrimidine-5-carboxylic acid (Maybridge, 138 mg, 1.0 mmol) with oxalyl chloride (Aldrich, 2 M, in CH2Cl2, 1.0 mL, 2.0 mmol) and a drop of dimethylformamide at room temperature over 1 hour with subsequent removal of volatiles under reduced pressure. 1H NMR (300 MHz, DMSO-d6) δ 7.72 (dt, J=10.5, 8.5 Hz, 1H), 7.94-8.05 (m, 1H), 8.11 (ddd, J=10.9, 7.7, 2.0 Hz, 1H), 8.12 (none, 1H), 9.51 (s, 1H), 9.54 (s, 2H) ppm; MS (DCI/NH3) m/z 261 (M+H)+.
Reaction SMILES: C[O:2][C:3](=[O:19])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15](I)=[CH:14][CH:13]=2)[CH:5]=1.O1CCOCC1.C(=O)([O-])[O-].[K+].[K+].[NH2:32][C:33]([C:35]1[CH:36]=[C:37](B(O)O)[CH:38]=[CH:39][CH:40]=1)=[O:34]>O>[C:33]([C:35]1[CH:40]=[C:39]([C:15]2[CH:16]=[CH:17][C:12]([O:11][CH2:10][C:6]3[CH:5]=[C:4]([CH:9]=[CH:8][CH:7]=3)[C:3]([OH:2])=[O:19])=[CH:13][CH:14]=2)[CH:38]=[CH:37][CH:36]=1)(=[O:34])[NH2:32]
Reactant: NC(=O)c1cccc(B(O)O)c1
Reactant: COC(=O)c1cccc(COc2ccc(I)cc2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: NC(=O)c1cccc(-c2ccc(OCc3cccc(C(=O)O)c3)cc2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A first stock solution was prepared consisting of 3-(4-iodo-phenoxymethyl)-benzoic acid methyl ester (of Intermediate 1; 1.11 g, 3 mmol), bis(tri-cyclohexyl-phosphine)palladium (available from Strem Chemicals, Inc., Newburyport, Mass.; 105 mg, 0.16 mmol), and dioxane (approximately 62 mL). A second stock solution was prepared consisting of potassium carbonate (1.245 g, 9 mmol) and water (approximately 6.2 mL). The solutions were sonicated and degassed by bubbling nitrogen gas through them. 4 mL of the first stock solution and 0.4 mL of the second stock solution were added to a reaction vial containing (3-aminocarbonylphenyl)boronic acid (available from Apollo Scientific Ltd., Stockport, UK; 99 mg, 0.6 mmol). The mixture was heated in a microwave oven at 170 degrees for 25 min and then passed through a silica gel column (1 g of silica), and washed with dioxane (1 mL) and dimethylacetamide (1 mL). 2 M potassium hydroxide solution (0.4 mL) was added. The mixture was stirred at room temperature overnight, and then 1 M HCl (0.8 mL) was added and the solvents were removed in the Genevac. Aqueous methanol (50%; approximately 2 mL) was added, then the vial was centrifuged and the solvent was removed. This process was repeated to give 3-(3′-carbamoyl-biphenyl-4-yloxymethyl)-benzoic acid. Mass spectrum MH+=348.
Reaction SMILES: [CH2:1]=[CH:2][CH2:3][CH2:4][CH2:5][CH3:6].[C:7]([O:11][CH3:12])(=[O:10])[CH:8]=[O:9]>>[OH:9][CH:8]([CH2:1][CH:2]=[CH:3][CH2:4][CH2:5][CH3:6])[C:7]([O:11][CH3:12])=[O:10]
Reactant: C=CCCCC
Reactant: COC(=O)C=O
Product: CCCC=CCC(O)C(=O)OC

Procedure:
The synthesis of this acid is in accordance with the following scheme, in which 1-hexene (22) is the alkene starting material which is reacted with methyl glyoxalate to form methyl 2-hydroxy-4-octenoate (23) and then hydrolysed to form the free acid (21): ##STR13##
Reaction SMILES: O.[NH:2]1[C:10](=[O:11])[C:8](=[O:9])[C:6](=[O:7])[NH:5][C:3]1=[O:4].[CH3:12][N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:15]=[CH:14]1>C(O)C>[OH:9][C:8]1([C:15]2[C:16]3[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:13]([CH3:12])[CH:14]=2)[C:6](=[O:7])[NH:5][C:3](=[O:4])[NH:2][C:10]1=[O:11]
Reactant: O=C1NC(=O)C(=O)C(=O)N1
Reactant: Cn1ccc2ccccc21
Solvent: CCO
Solvent: O
Product: Cn1cc(C2(O)C(=O)NC(=O)NC2=O)c2ccccc21

Procedure:
Alloxan hydrate (1.6 g., 0.01 mole) 1-methylindole (1.3 g., 0.01 mole) and ethanol (50 ml.) was combined and the mixture refluxed for 0.5 hour, then concentrated to half-volume, diluted with water and the resulting product recovered by filtration [2.7 g., Rf 0.5 (1:1 ethyl acetate:hexane/5% acetic acid)].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([CH3:12])=[C:6]2[CH2:13][C:14]([O:16][CH3:17])=[O:15].[H-].[Na+].Cl[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([S:28][CH3:29])=[CH:24][CH:23]=1>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([S:28][CH3:29])=[CH:24][CH:23]=1)[C:7]([CH3:12])=[C:6]2[CH2:13][C:14]([O:16][CH3:17])=[O:15]
Reactant: COC(=O)Cc1c(C)[nH]c2ccc(OC)cc12
Reactant: CSc1ccc(CCl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)Cc1c(C)n(Cc2ccc(SC)cc2)c2ccc(OC)cc12
Reaction time: 0.08 h
Yield: 48.6 %

Procedure:
To the indole of Example 7, Step 1, (1.00 g, 4.29 mmol) in DMF (15.0 mL) at 0° C. were added NaH 60% in oil (188 mg, 4.72 mmol) and a solution of 4-chloromethylthioanisole (810 mg, 4.7 mmol) in DMF (5.0 mL). After a period of 5 min at r.t., the reaction was quenched by the addition of 25% aqueous solution of NH4OAc. The reaction was extracted with EtOAc, dried over Na2SO4, evaporated in vacuo and purified by flash chromatography (20% EtOAc in hexane) to provide the title compound (770 mg).
Reaction SMILES: [CH3:1][C:2]1([C:7]2[O:11][C:10]([CH2:12][N:13]3[CH:17]=[CH:16][C:15]([NH2:18])=[N:14]3)=[CH:9][CH:8]=2)[O:6]CCO1.[C:19]([O:23][C:24]([NH:26][CH2:27][C:28]1[O:29][C:30]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[C:31]([C:33](O)=[O:34])[N:32]=1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>>[C:19]([O:23][C:24](=[O:25])[NH:26][CH2:27][C:28]1[O:29][C:30]([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)=[C:31]([C:33](=[O:34])[NH:18][C:15]2[CH:16]=[CH:17][N:13]([CH2:12][C:10]3[O:11][C:7]([C:2](=[O:6])[CH3:1])=[CH:8][CH:9]=3)[N:14]=2)[N:32]=1)([CH3:22])([CH3:20])[CH3:21]
Reactant: CC(C)(C)OC(=O)NCc1nc(C(=O)O)c(-c2ccccc2)o1
Reactant: CC1(c2ccc(Cn3ccc(N)n3)o2)OCCO1
Product: CC(=O)c1ccc(Cn2ccc(NC(=O)c3nc(CNC(=O)OC(C)(C)C)oc3-c3ccccc3)n2)o1

Procedure:
Following general procedure B followed by C starting from 1-[5-(2-methyl-[1,3]dioxolan-2-yl)-furan-2-ylmethyl]-1H-pyrazol-3-ylamine and 2-(tert-butoxycarbonylamino-methyl)-5-phenyl-oxazole-4-carboxylic acid. LC-MS-conditions 02: tR=1.03 min; [M+H]+=506.46.
Reaction SMILES: [C:1]([Br:5])(Br)(Br)[Br:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.[F:32][C:33]1[CH:40]=[CH:39][C:36]([CH:37]=O)=[C:35]([OH:41])[CH:34]=1>ClCCl>[Br:2][C:1]([Br:5])=[CH:37][C:36]1[CH:39]=[CH:40][C:33]([F:32])=[CH:34][C:35]=1[OH:41]
Reactant: O=Cc1ccc(F)cc1O
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Oc1cc(F)ccc1C=C(Br)Br
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 27.4 %

Procedure:
To a solution of CBr4 (5.6 g, 17.1 mmoL) in dichloromethane (100 mL) was added PPh3 (7 g, 26.69 mmol) at 0° C., 30 min later, NEt3 (4.3 g, 42.6 mmol) and 4-fluoro-2-hydroxybenzaldehyde (1 g, 7.14 mmol) was added slowly. After stirring for 30 mins at room temperature, the resulting mixture was concentrated under reduced pressure to afford a residue, which was purified by a silica gel column with 5% ethyl acetate in petroleum ether to afford 2-(2,2-dibromoethenyl)-5-fluorophenol as a white solid (0.58 g, 27%).
Reaction SMILES: [OH:1][C:2]1[N:7]2[N:8]=[C:9]([CH3:16])[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:6]2[CH:5]=[C:4]([CH3:17])[CH:3]=1.[Cl:18][C:19]1[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[C:20]=1[CH2:21]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[CH2:14]([O:13][C:11]([C:10]1[C:9]([CH3:16])=[N:8][N:7]2[C:2]([O:1][CH2:21][C:20]3[C:23]([F:27])=[CH:24][CH:25]=[CH:26][C:19]=3[Cl:18])=[CH:3][C:4]([CH3:17])=[CH:5][C:6]=12)=[O:12])[CH3:15]
Reactant: OCc1c(F)cccc1Cl
Reactant: CCOC(=O)c1c(C)nn2c(O)cc(C)cc12
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCOC(=O)c1c(C)nn2c(OCc3c(F)cccc3Cl)cc(C)cc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 84 %

Procedure:
A solution of 180 mg (0.76 mmol) of 7-hydroxy-2,5-dimethylpyrazolo[1,5-a]pyridine-3-carboxylic acid ethyl ester (Example 8A) in 7 ml of tetrahydrofuran was admixed with 247 mg (1.52 mmol) of 2-chloro-6-fluorobenzyl alcohol, 419 mg (1.60 mmol) of triphenylphosphine and 0.32 ml (1.60 mmol) of diisopropyl azodicarboxylate. The reaction mixture was stirred at room temperature for 1 h and concentrated under reduced pressure. The residue was purified by flash chromatography using a prepacked silica gel cartridge (mobile phase: cyclohexane-ethyl acetate, gradient 10% to 30%), which gave 280 mg (84% yield, 84% pure) of the target compound.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][CH2:9][CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.Cl[C:24]1[C:25]2[C:35]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=3[O:42][CH3:43])=[CH:34][S:33][C:26]=2[N:27]=[C:28]([CH:30]2[CH2:32][CH2:31]2)[N:29]=1>C(O)C>[CH:30]1([C:28]2[N:29]=[C:24]([N:13]3[CH2:14][CH2:15][CH:10]([CH2:9][O:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH2:11][CH2:12]3)[C:25]3[C:35]([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=4[O:42][CH3:43])=[CH:34][S:33][C:26]=3[N:27]=2)[CH2:32][CH2:31]1
Reactant: COc1ccccc1-c1csc2nc(C3CC3)nc(Cl)c12
Reactant: C1CCN(CCOCC2CCNCC2)C1
Solvent: CCN(CC)CC
Solvent: CCO
Product: COc1ccccc1-c1csc2nc(C3CC3)nc(N3CCC(COCCN4CCCC4)CC3)c12
Yield: 19 %

Procedure:
4-(2-Pyrrolidin-1-ylethoxymethyl)piperidine (0.10 g, 0.47 mmol), triethylamine (0.089 mL, 0.63 mmol) and 4-chloro-2-cyclopropyl-5-(2-methoxyphenyl)thieno[2,3-d]pyrimidine (0.10 g, 0.32 mmol) were combined and heated to 50° C. in ethanol (10 mL) overnight. The solvent was removed at reduced pressure. The residue was taken up in DCM (20 mL), washed with water (20 mL) and the organic dried over Na2SO4 and concentrated at reduced pressure. The resulting residue was purified by flash chromatography, eluting with a gradient of DCM to 90/10/1 DCM/MeOH/NH4OH to afford 2-cyclopropyl-5-(2-methoxyphenyl)-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidine (0.03 g). LCMS: purity 100%, RT=3.62 min, M+1=493.1