Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH2:2]([O:4][C:5]([N:7]1[CH2:12][CH2:11][C:10]([NH2:16])([CH2:13][CH2:14][NH2:15])[CH2:9][CH2:8]1)=[O:6])[CH3:3].C[O-].[Na+].[N:20]#[C:21][Br:22]>CO>[BrH:22].[CH2:2]([O:4][C:5]([N:7]1[CH2:12][CH2:11][C:10]2([NH:16][C:21]([NH2:20])=[N:15][CH2:14][CH2:13]2)[CH2:9][CH2:8]1)=[O:6])[CH3:3]
Reactant: N#CBr
Reactant: CCOC(=O)N1CCC(N)(CCN)CC1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: Br
Product: CCOC(=O)N1CCC2(CCN=C(N)N2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.6 %

Procedure:
To a solution of 15.65 g (54.33 mmol) of 4-amino-4-(2-amino-ethyl)-piperidine-1-carboxylic acid ethyl ester hydrochloride (2:1) in 108 ml of methanol was added 21.73 ml (114.09 mmol) of a solution of sodium methoxide in methanol (5.55 N). The mixture was stirred at room temperature for 2 h. The precipitate was filtered and the filtrate was evaporated. The crude was dissolved in 108 ml of water and 5.75 g (54.33 mmol) of cyanogen bromide was added portion wise. The resulting mixture was stirred at room temperature for 16 h, evaporated to dryness, dissolved in ethanol and evaporated to dryness to give 17.56 g of pure compound as a brown solid.
Reaction SMILES: [S:1]([C:5]1[CH:39]=[CH:38][C:8]([CH2:9][CH2:10][NH:11][CH2:12][C:13]2[N:14]([CH2:18][C:19]([N:21]([CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[O:20])[CH:15]=[CH:16][N:17]=2)=[CH:7][CH:6]=1)(=[O:4])(=[O:3])[NH2:2].[C:40]([O:44][C:45](=[O:78])[CH2:46][CH2:47][C:48]([NH:67][C:68](=[O:77])[CH2:69][N:70]1[CH:74]=[CH:73][N:72]=[C:71]1[CH:75]=O)([CH2:58][CH2:59][C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[CH2:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])([CH3:43])([CH3:42])[CH3:41].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl.O>[C:26]([O:25][C:23](=[O:24])[CH2:22][N:21]([CH2:30][C:31](=[O:32])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:19](=[O:20])[CH2:18][N:14]1[CH:15]=[CH:16][N:17]=[C:13]1[CH2:12][N:11]([CH2:75][C:71]1[N:70]([CH2:69][C:68]([NH:67][C:48]([CH2:58][CH2:59][C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])([CH2:47][CH2:46][C:45]([O:44][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:78])[CH2:49][CH2:50][C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[O:77])[CH:74]=[CH:73][N:72]=1)[CH2:10][CH2:9][C:8]1[CH:38]=[CH:39][C:5]([S:1](=[O:3])(=[O:4])[NH2:2])=[CH:6][CH:7]=1)([CH3:27])([CH3:28])[CH3:29]
Reactant: CC(C)(C)OC(=O)CN(CC(=O)OC(C)(C)C)C(=O)Cn1ccnc1CNCCc1ccc(S(N)(=O)=O)cc1
Reactant: CC(C)(C)OC(=O)CCC(CCC(=O)OC(C)(C)C)(CCC(=O)OC(C)(C)C)NC(=O)Cn1ccnc1C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O
Solvent: ClCCCl
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)CCC(CCC(=O)OC(C)(C)C)(CCC(=O)OC(C)(C)C)NC(=O)Cn1ccnc1CN(CCc1ccc(S(N)(=O)=O)cc1)Cc1nccn1CC(=O)N(CC(=O)OC(C)(C)C)CC(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 8 h
Yield: 61 %

Procedure:
To a solution of di-tert-butyl 2,2′-((2-(2-(((4-sulfamoylphenethyl)amino)methyl)-1H-imidazol-1-yl)acetyl)azanediyl)diacetate (200 mg, 0.353 mmol), di-tert-butyl 4-(3-(tert-butoxy)-3-oxopropyl)-4-(2-(2-formyl-1H-imidazol-1-yl)acetamido)heptanedioate (195 mg, 0.353 mmol), AcOH (0.10 mL) in DCE (10 mL) at 0° C. was treated with NaBH(OAc)3 (148 mg, 0.70 mmol). The reaction mixture was stirred at 0° C. for 30 minutes and at room temperature for overnight and decomposed with water. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by biotage over silica gel to afford di-tert-butyl 4-(2-(2-((((1-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)-2-oxoethyl)-1H-imidazol-2-yl)methyl)(4-sulfamoylphenethyl)amino)methyl)-1H-imidazol-1-yl)acetamido)-4-(3-(tert-butoxy)-3-oxopropyl)heptanedioate (237 mg, 61%). 1H NMR (400 MHz, DMSO-d6) 7.76 (s, 1H), 7.66 (d, J=8.4 Hz, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.22 (s, 2H), 7.01 (d, J=1.2 Hz, 1H), 6.99 (d, J=1.6 Hz, 2H), 6.83 (d, J=0.8 Hz, 1H), 6.80 (d, J=0.8 Hz, 1H), 5.02 (s, 2H), 4.55 (s, 2H), 4.31 (s, 2H), 3.97 (s, 2H), 3.63 (s, 2H), 3.60 (s, 2H), 2.77-2.73 (m, 2H), 2.66-2.60 (m, 2H), 2.10 (t, J=8.2 Hz, 6H), 1.78 (t, J=8.2 Hz, 6H), 1.36 (s, 45H); MS (ESI), 551.4 (M/2+H)+.
Reaction SMILES: [CH2:1]([C:8]1[C:9]([NH:22][C:23](=[S:33])[CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31]C)=[CH:27][CH:26]=2)=[N:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([O:20]C)=[CH:16][CH:15]=2)[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+].CCCCCC>ClCCl.C(OCC)(=O)C>[CH2:1]([C:8]1[C:9]([NH:22][C:23](=[S:33])[CH2:24][C:25]2[CH:26]=[CH:27][C:28]([OH:31])=[CH:29][CH:30]=2)=[N:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)[N:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(CC(=S)Nc2ncc(-c3ccc(OC)cc3)nc2Cc2ccccc2)cc1
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Oc1ccc(CC(=S)Nc2ncc(-c3ccc(O)cc3)nc2Cc2ccccc2)cc1
Temperature: 25 °C
Yield: 66.4 %

Procedure:
Under an argon atmosphere, 3-benzyl-5-(4-methoxyphenyl)-2-[(4-methoxyphenyl)thioacetylamino]pyrazine (c-44) (823 mg, 1.81 mmol) was dissolved in anhydrous dichloromethane (30 mL) and to this was added 1.0 M solution of boron tribromide in dichloromethane (6.80 mL, 6.80 mmol) at room temperature and heated to reflux for 21 h. After cooling to room temperature, to this was added saturated aqueous solution of sodium bicarbonate and concentrated under reduced pressure with a rotary evaporator to remove dichloromethane. The resulting suspension was filtrated and the residue was dried to give the crude product (591 mg) as a red solid. The crude product was dissolved in ethyl acetate and to this was added n-hexane to form a precipitate. The solid was collected by filtration and dried in vacuo to give 3-benzyl-5-(4-hydroxyphenyl)-2-[(4-hydroxyphenyl)thioacetylamino]pyrazine (coelenterathioamide) (c-45) as an orange solid (514 mg, 66.6%). Rf=0.23 (n-hexane/ethyl acetate=1/1). Mp. 101-103° C. 1H NMR (400 MHz, DMSO-d6) δ 3.90 (s, 2H), 4.00 (s, 2H), 6.71-6.77 (AABB′, 2H), 6.85-6.91 (AA′BB′, 2H), 6.97-7.03 (AA′BB′, 2H), 7.12-7.25 (m, 3H), 7.27-7.34 (m, 2H), 7.94-8.00 (AA′BB′, 2H), 8.91 (s, 1H), 9.34 (s, 1H), 9.94 (s, 1H), 12.05 (s, 1H). 13C NMR (67.8 MHz, DMSO-d6) δ 50.9, 115.1 (2C), 115.8 (2C), 126.0, 126.2, 127.0, 128.18 (2C), 128.24 (2C), 128.9 (2C), 129.9 (2C), 137.4, 138.0, 144.6, 149.9, 152.0, 156.4, 159.3, 205.3 (one carbon at benzyl position was unobservable due to over lapping with septet peak of DMSO). IR (KBr, cm−1) 515, 561, 706, 731, 837, 908, 935, 1063, 1130, 1171, 1238, 1315, 1371, 1443, 1514, 1609, 2808, 3026, 3159. HRMS (ESI+) m/z 428.1434 ((M+H)+, C25H22N3O2S+ requires 428.1427).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17](I)[CH:16]=1.B(O)(O)[C:24]1[CH:25]=[CH:26][C:27]([CH3:30])=[CH:28][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14]([C:15]1[CH:16]=[C:17]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)[CH:18]=[CH:19][CH:20]=1)=[O:22]
Reactant: Cc1ccc(B(O)O)cc1
Reactant: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1cccc(I)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: Cc1ccc(-c2cccc(C(=O)NCCc3c[nH]c4ccc(Cl)cc34)c2)cc1
Yield: 81.8 %

Procedure:
N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4′-methylbiphenyl-3-carboxamide was prepared according to method B with N-(2-(5-chloro-1H-indol-3-yl)ethyl)-3-iodobenzamide (0.075 g; 0.176 mmol), p-tolylboronic acid (0.025 g; 0.176 mmol), tetrakis(triphenylphosphine)palladium (0.010 g; 0.009 mmol), sodium carbonate (0.037 g; 0.353 mmol), in dimethoxyethane (3 mL) and water (1 mL), irradiated in a microwave oven at 130° C. for 15 minutes. Flash chromatography on silica gel (eluent 2 to 10% ethyl acetate in dichloromethane) furnished 0.056 g (82%) of N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4′-methylbiphenyl-3-carboxamide as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:12]3[C:13]([CH3:19])=[CH:14][C:15]([CH3:18])=[C:16]([CH3:17])[C:11]=3[O:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1>C(OCC)(=O)C.CCCCCC>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:12]3[C:13]([CH3:19])=[CH:14][C:15]([CH3:18])=[C:16]([CH3:17])[C:11]=3[O:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cc(C)c2c(-c3cccc(Br)c3)coc2c1C
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Cc1cc(C)c2c(c1C)OCC2c1cccc(Br)c1
Yield: 82 %

Procedure:
Using 3-(3-bromophenyl)-4,6,7-trimethyl-1-benzofuran obtained in Reference Example 186, the title compound was synthesized in the same manner as in Reference Example 199. Yield 82%. Melting point: 73-74° C. (ethyl acetate-hexane).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C@H:8]2[C@H:17]([OH:18])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([OH:19])[CH:15]=3)[O:10][CH2:9]2)[CH:2]=1.[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27]Br)[N:22]=1>>[Cl:20][C:21]1[N:22]=[C:23]([CH2:27][O:19][C:14]2[CH:15]=[C:16]3[C:11](=[CH:12][CH:13]=2)[O:10][CH2:9][C@@H:8]([CH2:7][C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[C@@H:17]3[OH:18])[CH:24]=[CH:25][CH:26]=1
Reactant: Oc1ccc2c(c1)[C@@H](O)[C@H](Cc1cccnc1)CO2
Reactant: Clc1cccc(CBr)n1
Product: O[C@@H]1c2cc(OCc3cccc(Cl)n3)ccc2OC[C@H]1Cc1cccnc1

Procedure:
By the method of Example 5, 500 mg (1.95 mmol) of trans-3-(3-pyridyl)methyl-4,6-chromandiol and 442 mg (2.14 mmol) of 2-chloro-6-(bromomethyl)pyridine were converted to present title product, purified by flash chromatography on a silica gel column using isopropyl alcohol:ethyl acetate:CH2Cl2, 1:2:17 as eluant, to yield 0.11 g (14%) of present title compound as a glass.
Reaction SMILES: [C:1]([O:5][C:6](=[O:39])[NH:7][C:8]1[C:13]2[C:14]([O:36][CH3:37])=[N:15][N:16]([C:17]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]=2[CH:11]=[C:10]([Cl:38])[N:9]=1)([CH3:4])([CH3:3])[CH3:2].[C:40]([O-])([O-])=O.[Cs+].[Cs+].IC.[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6](=[O:39])[N:7]([C:8]1[C:13]2[C:14]([O:36][CH3:37])=[N:15][N:16]([C:17]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:12]=2[CH:11]=[C:10]([Cl:38])[N:9]=1)[CH3:40])([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(Cl)nc(NC(=O)OC(C)(C)C)c12
Reactant: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Cs+]
Agent: [NH4+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CI
Product: COc1nn(C(c2ccccc2)(c2ccccc2)c2ccccc2)c2cc(Cl)nc(N(C)C(=O)OC(C)(C)C)c12
Temperature: 60 °C
Reaction time: 2 h

Procedure:
t-Butyl(6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)carbamate (45B, 86 mg, 0.159 mmol) was taken up in DMF (1.6 ml). Cs2CO3 (104 mg, 0.318 mmol) followed by iodomethane (10.93 μl, 0.175 mmol) were added. The reaction was allowed to stir at 60° C. for 2 hours. EtOAc and saturated NH4Cl were added. The products were extracted into EtOAc (3×). The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo to give tert-butyl(6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)(methyl)carbamate (46B). Reaction products were carrried forward without purification. MS: [M+H]+ m/z 555.
Reaction SMILES: [F:1][C:2]1[CH:35]=[CH:34][CH:33]=[CH:32][C:3]=1[C:4]([C:6]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:7]=1[NH:15][C:16]([C:18]([NH:21][C:22](=[O:31])[O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([CH3:20])[CH3:19])=[O:17])=[O:5].[C:36]([O-])(C)(C)C.[K+].CI.C(O)(=O)C>C(O)(C)(C)C>[F:1][C:2]1[CH:35]=[CH:34][CH:33]=[CH:32][C:3]=1[C:4]([C:6]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:7]=1[N:15]([CH3:36])[C:16]([C:18]([NH:21][C:22](=[O:31])[O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([CH3:19])[CH3:20])=[O:17])=[O:5]
Reactant: CC(C)(C)[O-]
Reactant: CC(C)(NC(=O)OCc1ccccc1)C(=O)Nc1ccc([N+](=O)[O-])cc1C(=O)c1ccccc1F
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: CI
Solvent: CC(=O)O
Product: CN(C(=O)C(C)(C)NC(=O)OCc1ccccc1)c1ccc([N+](=O)[O-])cc1C(=O)c1ccccc1F
Temperature: 25 °C
Reaction time: 60 h

Procedure:
A solution of 500 mg of benzyl [1-[[2-(o-fluorobenzoyl)-4-nitrophenyl]-carbamoyl]-1-methyl-ethyl]carbamate (1.043 mol) and 150 mg of potassium t-butanolate in 20 ml of t-butanol is treated with 0.15 ml of methyl iodide and stirred at room temperature for 2.5 days. The reaction mixture is buffered with glacial acetic acid and concentrated. The residue is partitioned between methylene chloride and 10 percent aqueous sodium bicarbonate solution. After drying the organic phase overnight and concentrating, the residue is chromatographed on a pressure column containing 10 g of silica gel (particle size 0.04-0.06 mm) under 0.2-0.4 atmospheres of nitrogen with methylene chloride/ethyl acetate (20:1) as the elution agent. There is obtained benzyl [1-[[2-(o-fluorobenzoyl)-4-nitrophenyl]-methylcarbamoyl]-1-methyl-ethyl]carbamate of melting point 168°-169° (ether/n-hexane).
Reaction SMILES: C[C:2]([O-:5])(C)C.[K+].[NH2:7][C:8]1[N:13]=[C:12]([O:14][CH3:15])[N:11]=[C:10]([CH3:16])[N:9]=1.C(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1.[NH2:33][S:34]([C:37]1[CH:46]=[C:45]([I:47])[CH:44]=[CH:43][C:38]=1[C:39]([O:41][CH3:42])=[O:40])(=[O:36])=[O:35]>CC(N(C)C)=O>[CH3:15][O:14][C:12]1[N:11]=[C:10]([CH3:16])[N:9]=[C:8]([NH:7][C:2]([NH:33][S:34]([C:37]2[CH:46]=[C:45]([I:47])[CH:44]=[CH:43][C:38]=2[C:39]([O:41][CH3:42])=[O:40])(=[O:36])=[O:35])=[O:5])[N:13]=1
Reactant: COc1nc(C)nc(N)n1
Reactant: COC(=O)c1ccc(I)cc1S(N)(=O)=O
Reactant: CC(C)(C)[O-]
Agent: O=C(Oc1ccccc1)Oc1ccccc1
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: COC(=O)c1ccc(I)cc1S(=O)(=O)NC(=O)Nc1nc(C)nc(OC)n1

Procedure:
2.59 g of potassium tert-butylate was added to a suspension of 2.85 g of 2-amino-4-methoxy-6-methyl-1,3,5-triazine in 40 ml of dimethylacetamide (DMA) at room temperature to form a first mixture. A solution of 4.94 g of diphenyl carbonate in 20 ml of DMA was then added dropwise to the first mixture at about 5° C. to form a second mixture. The second mixture was subsequently added dropwise to a solution of 5.00 g of methyl 2-aminosulfonyl-4-iodobenzoate (92.5% pure) in 15 ml of DMA at about 5° C., to form a third mixture. When the reaction ended, the third mixture was filtered over kieselguhr (®Celite). The filtrate was introduced into a solution of 200 ml of ice-water and 10 ml of concentrated hydrochloric acid, whereby the crude urea product separated out. The crude product which separated out was then purified by stirring with methanol and diisopropyl ether and dried. The yield was 4.50 g (66% of theory).
Reaction SMILES: [H-].[Na+].[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[C@@H:8]([OH:13])[CH2:9][CH2:10][CH2:11][CH3:12].Br[CH2:15][C:16]([OH:18])=[O:17]>C1COCC1>[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[CH:8]([CH2:9][CH2:10][CH2:11][CH3:12])[O:13][CH2:15][C:16]([OH:18])=[O:17]
Reactant: O=C(O)CBr
Reactant: CCCC[C@H](O)c1ccco1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCC(OCC(=O)O)c1ccco1
Temperature: 0 °C

Procedure:
NaH (16.3 g, 680.9 mmol) and freshly distilled THF (170 mL) were stirred at room temperature as (S)-1-(2-furyl)-1-pentanol ([α]25D -17.2°, 30.0 g, 46.0 mmol) in THF (170 mL) was added dropwise. After the addition was complete, the mixture was stirred for 15 m before cautiously heating to reflux for 1 h. The mixture was cooled to 0° C. before adding dropwise a solution of bromoacetic acid (27.3 g, 196.5 mmol) in THF (40 mL). The mixture was refluxed 2 days before cooling and carefully pouring into 600 mL ice water. The aqueous was washed with ether and acidified with HCl to pH 4, and extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4, and evaporated to give a quantitative yield of crude product which was used in the next step without further purification.
Reaction SMILES: [N:1]([CH2:4][CH2:5][O:6][CH2:7][CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[N+]=[N-].C1(C)C=CC=CC=1>CO.[Pd]>[NH2:1][CH2:4][CH2:5][O:6][CH2:7][CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:14])([CH3:13])[CH3:15]
Reactant: CC(C)(C)OC(=O)NCCOCCN=[N+]=[N-]
Agent: [Pd]
Solvent: Cc1ccccc1
Solvent: CO
Product: CC(C)(C)OC(=O)NCCOCCN
Reaction time: 18.5 h

Procedure:
A solution of tert-butyl 2-(2-azidoethoxy)ethylcarbamate (52 g, 226 mmol) in methanol (500 mL) was added to a Parr vessel containing 10% palladium on carbon (4 g) which had been wetted with toluene (30 mL). The mixture was placed under hydrogen pressure (30 psi; 2.0×105 Pa). After 18.5 hours analysis by thin layer chromatography indicated that the reaction was not complete. Catalyst (0.5 g) was added and the hydrogenation was continued for an additional 4 hours. The reaction mixture was filtered through a layer of CELITE filter aid and a glass wool filter pad. The filter cake was rinsed with a mixture of isopropanol and methanol. The filtrate was concentrated under reduced pressure to provide tert-butyl 2-(2-aminoethoxy)ethylcarbamate.
Reaction SMILES: [CH2:1]([P:4]([C:9]1[CH:10]=[C:11]([CH:13]=[CH:14][CH:15]=1)N)([CH2:6][CH2:7]C)=[O:5])[CH2:2]C.C(P(=O)CC)C.IC1C=CC([N+:29]([O-])=O)=CC=1>>[CH2:1]([P:4]([C:9]1[CH:10]=[CH:11][C:13]([NH2:29])=[CH:14][CH:15]=1)([CH2:6][CH3:7])=[O:5])[CH3:2]
Reactant: CCCP(=O)(CCC)c1cccc(N)c1
Reactant: O=[N+]([O-])c1ccc(I)cc1
Agent: CC[PH](=O)CC
Product: CCP(=O)(CC)c1ccc(N)cc1

Procedure:
The title compound was prepared according to the procedures leading to 3-(dipropylphosphoryl) aniline (Compound 168C) starting with the commercially available diethyl phosphine oxide and 4-iodonitrobenzene. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.47 (dd, J=8.46, 10.48 Hz, 2H), 6.74 (dd, J=2.27, 8.59 Hz, 2H), 3.97 (br. s., 2H), 1.76-2.02 (m, 4H), 1.11 (td, J=7.71, 16.67 Hz, 6H); MS (ES+): m/z: 198.0939 [MH+]. HPLC: tR=0.83 min (UPLC TOF MS: polar—3 min).
Reaction SMILES: [C:1](=[O:4])([OH:3])[OH:2].[Na+:5].[C:6](=[O:9])([O-:8])[O-:7].C(=O)(O)O.[Na+]>O>[C:1](=[O:2])([O-:4])[O-:3].[Na+:5].[Na+:5].[C:6](=[O:7])([OH:9])[O-:8].[Na+:5]
Reactant: O=C(O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: O=C([O-])O

Procedure:
The sodium sesquicarbonate found in trona ore is a complex salt that is soluble in water and dissolves to yield approximately 5 parts by weight sodium carbonate (Na2CO3) and 4 parts sodium bicarbonate (NaHCO3), as shown in the above analysis. The trona ore is processed to remove the insoluble material, the organic matter and other impurities to recover the valuable alkali contained in the trona.
Reaction SMILES: CC1(C)O[O:3]1.[C:6]([O:19][CH:20]1[CH2:25][CH:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH:23][CH:22]([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:21]1)(=[O:18])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]>CC(C)=O>[C:6]([O:19][CH:20]1[CH2:21][CH:22]([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[N:23]([OH:3])[CH:24]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:25]1)(=[O:18])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CCCCCCCCCCCC(=O)OC1CC(c2ccccc2)NC(c2ccccc2)C1
Reactant: CC1(C)OO1
Solvent: CC(C)=O
Product: CCCCCCCCCCCC(=O)OC1CC(c2ccccc2)N(O)C(c2ccccc2)C1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 77.5 %

Procedure:
A solution of 590 mL (27.7 mmol) of dimethyldioxirane, 0.047M in acetone (prepared by the procedure of Eaton and Wicks, J. Org. Chem. 1988, 53, 5353) is added via a cannula to a 0° C. solution of 12.1 g (27.7 mmol) of 2,6-diphenyl-4-piperidyl laurate in 200 mL of acetone. After stirring for 10 minutes at 0° C., the reaction mixture is concentrated under reduced pressure and the residue is recrystallized from methanol to yield 9.7 g (78% yield) of the title compound as a white solid: mp 89°-90° C.
Reaction SMILES: N1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.C(Br)Br.[CH:16]12CC(CC1)C=[CH:17]2>C1(C)C=CC=CC=1>[CH:10]1[C:9]2[NH:8][C:7]3[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:17]=2[CH:16]=[CH:12][CH:11]=1
Reactant: c1ccc(-c2ccccn2)nc1
Reactant: C1=CC2CCC1C2
Solvent: Cc1ccccc1
Solvent: BrCBr
Product: c1ccc2c(c1)[nH]c1ccccc12
Temperature: 100 °C
Reaction time: 12 h

Procedure:
To an ampoule, Cu(I)Br (1 mmol), 2,2′-bipyridine (1 mmol), norbornene methylene bromide (NBMBr) (1 mmol) and styrene(St) (100 mmol) were added in 10 mL toluene. The heterogeneous mixture was placed under vacuum and then degassed via a freeze-pump-thaw cycle thrice. After degassing, the reaction mixture in ampoule was stirred at 100° C. for 12 hrs. The macromonomer containing polystyrene segments (NBMPStBr) was precipitated from methanol. Polymer was dissolved in THF and reprecipitated from methanol three times. Number average molecular weight of (NBMPStBr) is 160000 and PDI is 1.28 (by GPC).
Reaction SMILES: [I:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[C:10]([C:18]([OH:20])=O)[N:9]=2)[CH:5]=[CH:6][CH:7]=1.F[P-](F)(F)(F)(F)F.[N:28]1(O[P+](N(C)C)(N(C)C)N(C)C)[C:32]2C=CC=CC=2N=N1.Cl.CN.CCN(CC)CC>CN(C=O)C>[I:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=[C:10]([C:18]([NH:28][CH3:32])=[O:20])[N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)c1cc2ccccc2c(-c2cccc(I)c2)n1
Reactant: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: CN
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CNC(=O)c1cc2ccccc2c(-c2cccc(I)c2)n1
Temperature: 25 °C
Reaction time: 7 h
Yield: 47.7 %

Procedure:
To a mixture of 1-(3-iodophenyl)-3-isoquinolinecarboxylic acid (0.1186 g, 0.32 mmol), BOP (0.1402 g, 0.32 mmol), Methylamine hydrochloride (0.083 g, 1.23 mmol) in DMF (10 mL) was added Et3N (0.17 mL, 1.22 mmol). The resulting mixture was stirred under Ar at room temperature for 7 h and quenched by adding H2O (10 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were dried (MgSO4), filtered. The filtrate was concentrated in vacuo. The residue was purified on column (SiO2, 35% ethyl acetate/hexane, 0.1% Et3N), thereby giving a white solid (59.2 mg, 48%). mp 172.1-173.6° C. 1H NMR (CDCl3) d 3.03, 3.04 (two s, 3 H, N-methyl), 7.24 (t, J=8.7 Hz, 1 H, aromatic), 7.55-7.65 (m, 2 H, aromatic), 7.71 (t, J=8.1 Hz, 1 H, aromatic), 7.82 (d, J=8.7 Hz, 1 H, aromatic), 7.95-8.05 (m, 3 H, aromatic), 8.19 (br s, 1 H, CONH), 8.57 (s, 1 H, aromatic). 13C NMR (CDCl3) d 26.16 (q, N-methyl), 94.24 (s, C--I), 119.86 (d, aromatic), 127.15 (d, aromatic), 128.70 (d, aromatic), 128.96 (d, aromatic), 129.13 (d, aromatic), 129.91 (d, aromatic), 130.77 (d, aromatic), 137.14 (s, aromatic), 137.85 (d, aromatic), 138.57 (d, aromatic), 140.99 (s, aromatic), 142.67 (s, aromatic), 157.62 (s, aromatic), 165.25 (s, CO). HRMS calcd. for C17H13IN2O: 388.0073. Found: 388.0071.
Reaction SMILES: Cl[C:2]1[O:3][C:4]2[C:5](=[C:7]([C:19]#[N:20])[C:8]([CH3:18])=[C:9]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:10]=2[F:11])[N:6]=1.C(N(C(C)C)CC)(C)C.[NH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>ClCCl>[F:11][C:10]1[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:8]([CH3:18])[C:7]([C:19]#[N:20])=[C:5]2[C:4]=1[O:3][C:2]([N:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)=[N:6]2
Reactant: C1CCNCC1
Reactant: Cc1c(-c2ccccc2)c(F)c2oc(Cl)nc2c1C#N
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1c(-c2ccccc2)c(F)c2oc(N3CCCCC3)nc2c1C#N
Yield: 89.5 %

Procedure:
2-Chloro-7-fluoro-5-methyl-6-phenyl-1,3-benzoxazole-4-cabonitrile (I-130) (0.20 g, 0.70 mmol) was dissolved in dichloromethane (10 ml), and diisopropylethylamine (0.15 ml, 0.88 mmol) and piperidine (83.0 μl, 0.84 mmol) were added. This was heated under reflux for 3 hours, and diluted with dichloromethane. After washing with water and drying over anhydrous sodium sulfate, the solvent was evaporated away under reduced pressure, and the resulting residue was purified by silica gel column chromatography (dichloromethane) to obtain a colorless solid (0.21 g, 90%).