Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([OH:11])(=[O:10])/[CH:2]=[CH:3]/[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH2:12]([N+:22]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])([CH3:24])[CH3:23])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].C(Cl)(Cl)Cl>[Br-].C([N+](CCCCCCCCCC)(C)C)CCCCCCCCC.CS(C)=O>[C:1]([O-:11])(=[O:10])/[CH:2]=[CH:3]/[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1.[CH2:25]([N+:22]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])([CH3:24])[CH3:23])[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: O=C(O)/C=C/c1ccccc1
Agent: CCCCCCCCCC[N+](C)(C)CCCCCCCCCC
Agent: [Br-]
Solvent: CS(C)=O
Solvent: ClC(Cl)Cl
Product: O=C([O-])/C=C/c1ccccc1
Temperature: 90 °C
Reaction time: 4 h

Procedure:
Didecyldimethylammonium bromide (0.001 mol) was dissolved in 50 mL of hot distilled water. trans-Cinnamic acid (0.001 mol) was added to the didecyldimethylammonium solution. The reaction solution was stirred at 90° C. for 4 h. The reaction solution was cooled to room temperature and then 60 mL of chloroform was added. The two phases were separated and the chloroform phase was washed several times with cool distilled water to remove any inorganic salt. The presence of chloride anions was monitored by silver nitrate test. A rotary evaporator removed the chloroform and a wax was obtained in 93% yield. 1H and 13C NMR (DMSO) were obtained. Melting point (hot plate apparatus)=54-55° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:32]=[C:31]([N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)[CH:30]=[CH:29][C:16]=2[C:17]([NH:19][C:20]2[CH:24]=[CH:23][S:22][C:21]=2[C:25]([O:27]C)=[O:26])=[O:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCO.[OH-].[K+]>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:32]=[C:31]([N:33]3[CH2:34][CH2:35][CH2:36][CH2:37]3)[CH:30]=[CH:29][C:16]=2[C:17]([NH:19][C:20]2[CH:24]=[CH:23][S:22][C:21]=2[C:25]([OH:27])=[O:26])=[O:18])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1sccc1NC(=O)c1ccc(N2CCCC2)cc1OC1CCN(C(=O)OC(C)(C)C)CC1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)N1CCC(Oc2cc(N3CCCC3)ccc2C(=O)Nc2ccsc2C(=O)O)CC1
Yield: 94.4 %

Procedure:
A solution of the methyl 3-[2-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-4-(pyrrolidin-1-yl)benzoylamino]-thiophene-2-carboxylate (3.8 g, 7.2 mmol) and EtOH (100 mL) was treated with a solution of KOH (0.88 g) in water (80 mL). The reaction mixture was refluxed overnight, quenched with glacial acetic acid (1.5 mL) and concentrated under vacuum. The resulting aqueous mixture was extracted with EtOAc (2×100 mL). The combined extracts were dried over MgSO4 and concentrated to give 3.5 g (6.8 mmol, 94%) of the acid as a foam.
Reaction SMILES: [S:1]([N:11]1[C:19]2[CH:18]=[CH:17][N:16]=[C:15]([CH2:20][NH2:21])[C:14]=2[CH:13]=[N:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].Cl[C:23]1[N:28]=[C:27]([NH:29][C:30]2[CH:34]=[C:33]([CH:35]3[CH2:37][CH2:36]3)[NH:32][N:31]=2)[CH:26]=[CH:25][N:24]=1.CCN(C(C)C)C(C)C>CC(O)C>[CH:35]1([C:33]2[NH:32][N:31]=[C:30]([NH:29][C:27]3[CH:26]=[CH:25][N:24]=[C:23]([NH:21][CH2:20][C:15]4[C:14]5[CH:13]=[N:12][N:11]([S:1]([C:4]6[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=6)(=[O:3])=[O:2])[C:19]=5[CH:18]=[CH:17][N:16]=4)[N:28]=3)[CH:34]=2)[CH2:37][CH2:36]1
Reactant: Cc1ccc(S(=O)(=O)n2ncc3c(CN)nccc32)cc1
Reactant: Clc1nccc(Nc2cc(C3CC3)[nH]n2)n1
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(S(=O)(=O)n2ncc3c(CNc4nccc(Nc5cc(C6CC6)[nH]n5)n4)nccc32)cc1
Temperature: 120 °C
Yield: 76 %

Procedure:
A mixture of (1-tosyl-1H-pyrazolo[4,3-c]pyridin-4-yl)methanamine (300 mg, 1.3 mmol), 2-chloro-N-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-4-amine (258 mg, 1.05 mmol), and DIPEA (0.5 mL) in IPA (2 mL) was heated at 120° C. overnight. The reaction mixture was concentrated under reduced pressure to afford 400 mg (61%) of crude N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-((1-tosyl-1H-pyrazolo[4,3-c]pyridin-4-yl)methyl)pyrimidine-2,4-diamine as yellow oil. MS (ESI): m/z=502.3 [M+1]+.
Reaction SMILES: [F:1][C:2]1([F:11])[O:6][C:5]2[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=2[O:3]1.C1CCCCC1.[Li]C(CC)C.C[O:24][B:25](OC)[O:26]C>C1COCC1>[F:11][C:2]1([F:1])[O:3][C:4]2[CH:10]=[CH:9][CH:8]=[C:7]([B:25]([OH:26])[OH:24])[C:5]=2[O:6]1
Reactant: COB(OC)OC
Reactant: FC1(F)Oc2ccccc2O1
Agent: [Li]C(C)CC
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: OB(O)c1cccc2c1OC(F)(F)O2
Temperature: -78 °C
Reaction time: 1.5 h

Procedure:
2,2-Difluoro-1,3-benzodioxole (960 mg, 6.1 mmol) was dissolved in THF (8 mL) and cyclohexane (4 mL) and the resulting solution cooled to −78° C. sec-BuLi 1.4M solution in cyclohexane (4.3 mL, 6.1 mmol) was added dropwise and the reaction mixture stirred for 1.5 hours at −78° C. Trimethylborate (694 mg, 6.75 mmol) was added and the mixture was allowed to warm slowly to −30° C. The reaction mixture was quenched with a 2N solution of HCl and diluted with ethyl acetate. Two phases were separated and the organic layer was washed twice with brine, dried over Na2SO4 and evaporated to dryness affording the title compound as yellow oil which was used in the next step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH2:10])[C:5]([NH2:9])=[CH:6][C:7]=1[Cl:8].C1N=CN([C:16](N2C=NC=C2)=[O:17])C=1.O>CN(C=O)C>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][C:5]2[NH:9][C:16](=[O:17])[NH:10][C:4]=2[CH:3]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Nc1cc(Cl)c(Cl)cc1N
Solvent: O
Solvent: CN(C)C=O
Product: O=c1[nH]c2cc(Cl)c(Cl)cc2[nH]1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.5 %

Procedure:
To the solution of 4,5-dichloro-benzene-1,2-diamine (25 g, 0.14 mol) in dry DMF (200 mL), was added CDI (23 g, 0.14 mol) as the solid. The reaction solution was stirred at room temperature for 1 hour, then water (500 mL) was added. The precipitated solid was collected by filtration, washed with water, dried thoroughly to afford the titled compound (26.0 g, 90%). The crude product was used in the following reaction without further purification.
Reaction SMILES: [CH:1]1([CH3:13])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:9])[CH3:8])[CH:3]([C:10](Cl)=[O:11])[CH2:2]1.[NH:14]([CH2:18][CH2:19][OH:20])[CH2:15][CH2:16][OH:17]>C(Cl)(Cl)Cl>[OH:17][CH2:16][CH2:15][N:14]([CH2:18][CH2:19][OH:20])[C:10]([CH:3]1[CH:4]([CH:7]([CH3:9])[CH3:8])[CH2:5][CH2:6][CH:1]([CH3:13])[CH2:2]1)=[O:11]
Reactant: CC1CCC(C(C)C)C(C(=O)Cl)C1
Reactant: OCCNCCO
Solvent: ClC(Cl)Cl
Product: CC1CCC(C(C)C)C(C(=O)N(CCO)CCO)C1
Reaction time: 2 h

Procedure:
A solution of p-menth-3-oyl chloride (4.0 g., 0.020 moles) in chloroform (30 ml.) was added dropwise to a stirred solution of diethanolamine (4.2 g., 0.044 moles) in chloroform (50 ml.). The reaction mixture goes cloudy and a yellow oil separates out. After 2 hours at room temperature, the yellow oil (upper layer) was separated. Infra red spectrographic analysis indicated this to be (HOCH2CH2)2NH2+Cl-. Removal of the chloroform left a viscous oil (6 g.). Thin layer chromatography (CHCl3 and CHCl3 +10% CH3OH) indicated it to consist of one major component and a minor component of larger Rf value. This was separated by column chromatography on neutral alumina (activity 1). Eluting with chloroform (200 ml.) removed the minor component and the major product was eluted from the column with chloroform+5% methanol. The major component was shown to be N,N-bis(2-hydroxyethyl)-p-menthane -3-carboxamide.
Reaction SMILES: [CH2:1]([O:4][C:5](=[O:30])[CH2:6][CH2:7][CH:8]([NH:12][C:13]([O:15][CH2:16][CH:17]1[C:29]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:23]2[C:18]1=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:14])[C:9]([OH:11])=[O:10])[CH:2]=[CH2:3].[CH2:31](O)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.CCN=C=NCCCN(C)C.CN(C1C=CC=CN=1)C>C(Cl)Cl>[CH2:31]([O:10][C:9](=[O:11])[CH:8]([NH:12][C:13]([O:15][CH2:16][CH:17]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:23]=2[C:24]2[C:29]1=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:14])[CH2:7][CH2:6][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:30])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1
Reactant: OCc1ccccc1
Reactant: C=CCOC(=O)CCC(NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Product: C=CCOC(=O)CCC(NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)OCc1ccccc1
Temperature: 22 °C
Reaction time: 6 h
Yield: 10 %

Procedure:
Treatment with Fmoc-Cl followed by coupling to benzyl alcohol using 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide [by] hydrochloride (EDCl) provided 2-(9H-Fluoren-9-ylmethoxycarbonylamino)-pentanedioic acid 5-allyl ester 1-benzyl ester 6 in 82% yield. To a solution of 1.5 g (36.6 mmol) of 5 in 5 mL of CH2Cl2 was added 0.42 mL (40.3 mmol) of benzyl alcohol, 0.912 g (47.6 mmol) of EDCI, and 45 mg (3.66 mmol) of dimethylaminopyridine (DMAP). The reaction mixture was stirred at 22° C. for 6 h, diluted with 20 mL of CH2Cl2, and extracted with H2O(1×15 mL), 0.1M HCl (2×15 mL), and brine (2×10 mL). The organic layer was dried (Na2SO4), concentrated in vacuo, and chromatographed on SiO2 (Hexanes/EtOAc, 5:1) to give 1.83 g (82%) of 6 as a white solid: Mp 66.2-67.1° C. (EtOAc/Hexanes); [α]D +1.4° (c 1.64, CHCl3, 21° C.); IR (neat) 3314, 1726, 1682, 1527, 1443, 1414, 1383, 1254, 1173, 1099, 1082, 980, 754, 735 cm-1 ; 1H NMR δ 7.75 (d, 2 H, J=7.4 Hz), 7.59 (d, 2 H, J=7.1 Hz), 7.41-7.27 (m, 9 H), 5.95-5.85 (m, 1 H), 5.44 (d, 1 H, J=8.2 Hz), 5.34-5.19 (m, 4 H), 4.56 (d, 2 H, J=5.6 Hz), 4.5-4.4 (m, 3 H), 4.21 (t, 1 H, J=7.0 Hz), 2.5-2.0 (m, 4 H); 13C NMR δ 172.2, 171.6, 155.8, 143.7, 143.5, 141.1, 135.0, 131.8, 128.5, 128.3, 128.1, 127.6, 126.9, 124.9, 119.8, 118.3, 67.2, 66.9, 66.2, 53.3, 47.0, 28.0, 27.3; MS (FAB, MNBA/MeOH) m/z (relative intensity) 500 ([M+H]+, 40), 465 (8), 448 (14), 433 (12), 413 (8), 386 (38), 371 (24), 349 (9), 324 (16), 309 (26), 293 (11), 265 (10), 247 (24), 231 (56), 215 (39), 202 (26), 191 (24), 179 (67), 165 (48), 154 (67), 143 (31), 133 (71), 117 (100).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[CH3:12][C:13]([CH3:17])([CH3:16])[CH:14]=O.N1CCCC1>CO>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5](/[C:6](=[CH:12]\[C:13]([CH3:17])([CH3:16])[CH3:14])/[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1
Reactant: O=C1Cc2ccc(Cl)cc2N1
Reactant: CC(C)(C)C=O
Solvent: CO
Solvent: C1CCNC1
Product: CC(C)(C)/C=C1/C(=O)Nc2cc(Cl)ccc21

Procedure:
In a manner similar to the method described in example 1a, 6-chlorooxindole (0.88 g, 5 mmol) was reacted with 2,2-dimethyl-propionaldehyde (0.43 g, 5 mmol) (Aldrich), pyrrolidine (0.36 g, 5 mmol) in methanol to give a mixture of E- and Z-6-Chloro-3-(2,2-dimethyl-propylidene)-1,3-dihydro-indol-2-one. Purification by chromatography (EtOAc:hexanes=1:2) led to E-6-chloro-3-(2,2-dimethyl-propylidene)-1,3-dihydro-indol-2-one as an off-white foam (Yield 0.82 g, 70%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl[CH2:17][CH2:18][CH:19]([N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1)[CH3:20].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[N:21]1([CH:19]([CH3:20])[CH2:18][CH2:17][O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]3([C:14]#[N:15])[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: CC(CCCl)N1CCCC1
Reactant: N#CC1(c2ccc(O)cc2)CCOCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(CCOc1ccc(C2(C#N)CCOCC2)cc1)N1CCCC1
Yield: 9.4 %

Procedure:
4-(4-Hydroxy-phenyl)-tetrahydro-pyran-4-carbonitrile (1.0 g, 4.9 mmol), 1-(3-chloro-1-methyl-propyl)-pyrrolidine (780 mg, 3.90 mmol), DMF (20 ml) and K2CO3 (2.71 g, 19.60 mmol) were reacted together according to general procedure E. The organic phase was washed with 2M NaOH (3×20 ml), water (2×20 ml), dried over MgSO4, fitered and concentrated in vacuo at 35° C. and purified by preparative HPLC, eluting with acetonitrile/water/0.1% TFA as a gradient, to provide the title compound (120 mg, 9%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.38 (d, 2H), 6.93 (d, 2H), 4.15-3.98 (m, 4H), 3.89 (td, 2H), 2.75-2.51 (m, 5H), 2.22-1.74 (m, 10H), 1.17 (d, 3H).
Reaction SMILES: [F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][S:7]([CH2:10][C:11](O)=O)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[Br:16][C:17]1[CH:24]=[CH:23][C:20](C=O)=[CH:19][CH:18]=1>>[F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][S:7](/[CH:10]=[CH:11]/[C:20]2[CH:23]=[CH:24][C:17]([Br:16])=[CH:18][CH:19]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: O=C(O)CS(=O)(=O)Cc1ccc(F)cc1
Product: O=S(=O)(/C=C/c1ccc(Br)cc1)Cc1ccc(F)cc1
Yield: 82 %

Procedure:
A solution of 4-fluorobenzyl sulfonylacetic acid (0.01 mol) and 4-bromobenzaldehyde (0.01 mol) was subjected to Procedure 1. The title compound was obtained in 82% yield.
Reaction SMILES: [CH2:1]([Si:7]([CH3:10])(Cl)Cl)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH:11]1[C:23]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]=2[CH:14]=[CH:13][CH:12]=1>C1COCC1>[CH2:1]([Si:7]([CH3:10])([CH:22]1[C:23]2[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=2[C:16]2[C:21]1=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:22]1[C:21]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:15]2[C:23]1=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCC[Si](C)(Cl)Cl
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Solvent: C1CCOC1
Product: CCCCCC[Si](C)(C1c2ccccc2-c2ccccc21)C1c2ccccc2-c2ccccc21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
n-Hexylmethyldichlorosilane (30.4 g, 0.152 mol) and 300 mL of dry THF were charged to a one liter Schlenk equipped with an addition funnel. Fluorene anion (52.4 g, 0.305 mol) was dissolved in approximately 200 mL of dry THF and charged to the addition funnel. The temperature of the stirring solution was lowered to −78° C. under positive nitrogen pressure. The fluorene anion was added dropwise over two hours. After the anion addition was complete, the reaction mixture was allowed to warm to room temperature. The solution was allowed to stir overnight. The solution was washed with three 200 mL aliquots of water, retaining the organic layer after each washing. The organic layer was dried with magnesium sulfate and filtered. The product was recrystallized from hexane. The yield of this reaction is 19.6%.
Reaction SMILES: [Br:1][C:2]1[NH:6][C:5]2[CH:7]=[C:8]([Cl:13])[C:9]([Cl:12])=[C:10]([Cl:11])[C:4]=2[N:3]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.C(O[CH:30]1[O:42][C@H:41]([CH3:43])[C@@H:36]([O:37][C:38](=[O:40])[CH3:39])[C@H:31]1[O:32][C:33](=[O:35])[CH3:34])(=O)C.C[Si](OS(C(F)(F)F)(=O)=O)(C)C>C(#N)C.C(OCC)(=O)C>[Br:1][C:2]1[N:6]([C@@H:30]2[O:42][C@H:41]([CH3:43])[C@@H:36]([O:37][C:38](=[O:40])[CH3:39])[C@H:31]2[O:32][C:33](=[O:35])[CH3:34])[C:5]2[CH:7]=[C:8]([Cl:13])[C:9]([Cl:12])=[C:10]([Cl:11])[C:4]=2[N:3]=1
Reactant: Clc1cc2[nH]c(Br)nc2c(Cl)c1Cl
Reactant: CC(=O)OC1O[C@H](C)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Agent: C/C(=N\[Si](C)(C)C)O[Si](C)(C)C
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](C)O[C@H]1n1c(Br)nc2c(Cl)c(Cl)c(Cl)cc21
Temperature: 70 °C
Reaction time: 0.33 h
Yield: 57.9 %

Procedure:
2-Bromo4,5,6-trichloro-1H-benzimidazole (0.3 g, 1 mmol), acetonitrile (10 mL), and N,O-bis(trimethylsilyl)acetamide were stirred at 70° C. for 15 min., giving a homogeneous solution. To the solution was then added 1,2,3-tri-O-acetyl-5-deoxyribofuranose (0.31 g, 1.2 mmol) in acetonitrile (5 mL) and trimethylsilyltrifluoromethane sulfonate (0.25 mL, 1.3 mmol). The resulting mixture was allowed to stir at 70° C. for 20 min. The mixture was then allowed to cool to RT and was diluted with ethyl acetate and was washed with a saturated aqueous NaHCO3 solution, dried over NaSO4 and the solvents were removed by rotary evaporation. The product was purified by flash chromatography using chloroform as eluent and then recrystallization from methanol afforded 0.29 g (58%) of the title compound as white crystals; m.p. 160-162° C.; 1H NMR (DMSO-d6) δ: 8.14 (s, 1H), 6.16 (d, 1H), 5.63 (t, 1H), 5.27 (dd, 1H), 4.26 (m, 1H), 2.13 (s, 3H), 2.02 (s, 3H), 1.51 (d, 3H).
Reaction SMILES: C([N:8]([C@H:16]([C@@H:24]([OH:42])[CH2:25][C@@H:26]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)CC1C=CC=CC=1)C1C=CC=CC=1.C([O-])=O.[NH4+]>CCO.O.[Pd]>[NH2:8][C@H:16]([C@@H:24]([OH:42])[CH2:25][C@@H:26]([NH:34][C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])[CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C[C@H](O)[C@H](Cc1ccccc1)N(Cc1ccccc1)Cc1ccccc1
Agent: [Pd]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)C[C@H](O)[C@@H](N)Cc1ccccc1
Temperature: 25 °C

Procedure:
A solution of the product from Example 19C (150 gm, 250 mmol) dissolved in absolute EtOH (2 liters) was treated with 10% Pd/C (18 gm, pre-wetted), followed by addition of ammonium formate (78.6 gms, 1.25 moles) dissolved in H2O (200 ml). The resulting mixture was stirred at reflux for 2.5 hours. The mixture was cooled to room temperature and filtered through a pad of infusorial earth (20 g). The filter cake was washed 3 times with EtOH (70 ml each). The filtrate was concentrated in vacuo. The residue was dissolved into EtOAc (1L) and washed (1N NaOH, followed by H2O, followed by brine), dried (Na2SO4), filtered and concentrated in vacuo. to a constant weight of 95 gms. (99.2 % of theory). The light yellow solid (91.5 gm of the 95 gm) was slurried in hot heptane (600 ml) (steam bath) and treated with isopropanol (45 ml), and swirled to effect solution. The solution was allowed to slowly cool to room temperature over 3 hours, kept at room temperature for 2 more hours and filtered. The filter cake was washed 10 times with 9/1 hexane-isopropanol (30 ml each) to give the desired product as an off-white finely crystalline solid which was dried to constant weight of 57.5 gm.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[CH2:7][C:8]#[N:9])([O-:3])=[O:2].O.[C:14]([OH:18])(=[O:17])[CH:15]=O.C(=O)([O-])[O-].[K+:23].[K+]>CO>[K+:23].[C:8]([C:7]([C:6]1[CH:10]=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)=[CH:15][C:14]([O-:18])=[O:17])#[N:9]
Reactant: O=CC(=O)O
Reactant: N#CCc1cccc([N+](=O)[O-])c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: N#CC(=CC(=O)[O-])c1cccc([N+](=O)[O-])c1
Reaction time: 5 h
Yield: 85.1 %

Procedure:
A suspension of 3-nitrobenzyl cyanide (1.62 g), glyoxylic acid monohydrate (1.38 g) and potassium carbonate (3.59 g) in methanol (20 ml) was stirred for 5 hours. The precipitate was collected by filtration, washed with dichloromethane and dried. The precipitate was suspended in water and stirred for an hour. The insoluble material was collected by filtration and dried to give 3-cyano-3-(3-nitro-phenyl)-acrylic acid potassium salt (2.18 g, 85.2%).
Reaction SMILES: Br[CH2:2][C:3]1[C:12]([C:13]#[N:14])=[CH:11][CH:10]=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6].C1(=O)O[C:19](=[O:20])[C:18]2=[CH:22][CH:23]=[CH:24][CH:25]=[C:17]2[CH2:16]1.C(N(CC)CC)C>C(#N)C>[O:20]=[C:19]1[C:18]2[C:17](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:16]2[CH2:2][C:3]3[C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:9][CH:10]=[CH:11][C:12]=3[C:13]=2[NH:14]1
Reactant: COC(=O)c1cccc(C#N)c1CBr
Reactant: O=C1Cc2ccccc2C(=O)O1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COC(=O)c1cccc2c1Cc1c-2[nH]c(=O)c2ccccc12
Temperature: 25 °C
Yield: 81 %

Procedure:
A mixture of methyl 2-bromomethyl-3-cyanobenzoate (14.1 g, 55.5 mmol) and homophthalic anhydride (22.5 g, 138.8 mmol) in acetonitrile (150 ml) was stirred at room temperature, and a solution of triethylamine (23.2 ml) in acetonitrile (100 ml) was added dropwise to the mixture over the period of 1 h. After the completion of addition, the resultant suspension was refluxed for 4 hours. The reaction mixture was then cooled down to room temperature and filtered. The filtered solid was washed thoroughly with acetonitrile (100 ml) and ethanol (2×100 ml) and dried under vacuum at 50° C. Compound 17a was obtained in 81% yield (13.1 g). 1H NMR (DMSO-d6): δ 12.21 (s, 1H); 8.20 (m, 2H); 7.83 (d, J=7.5 Hz, 1H); 7.71 (m, 2H); 7.47 (m, 2H); 4.07 (s, 2H); 3.89 (s, 3H).
Reaction SMILES: [CH2:1]([C:9]1[CH:10]=[N:11][C:12]([C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)=[N:13][CH:14]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[F:22][C:23]([F:64])([C:60]([F:63])([F:62])[F:61])[C:24]([F:59])([F:58])[C:25]([F:57])([F:56])[O:26][C:27]([F:55])([F:54])[C:28]([F:53])([F:52])[O:29][C:30]([F:51])([F:50])[C:31]([F:49])([F:48])[C:32]([F:47])([F:46])[C:33]([F:45])([F:44])[C:34]([F:43])([F:42])[CH2:35][O:36][CH2:37][CH2:38][CH2:39][CH2:40]Br>>[CH2:1]([C:9]1[CH:14]=[N:13][C:12]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:40][CH2:39][CH2:38][CH2:37][O:36][CH2:35][C:34]([F:42])([F:43])[C:33]([F:44])([F:45])[C:32]([F:46])([F:47])[C:31]([F:48])([F:49])[C:30]([O:29][C:28]([F:52])([F:53])[C:27]([F:54])([F:55])[O:26][C:25]([F:56])([F:57])[C:24]([F:58])([F:59])[C:23]([F:64])([F:22])[C:60]([F:61])([F:63])[F:62])([F:51])[F:50])=[CH:17][CH:16]=2)=[N:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)COCCCCBr
Reactant: CCCCCCCCc1cnc(-c2ccc(O)cc2)nc1
Product: CCCCCCCCc1cnc(-c2ccc(OCCCCOCC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)OC(F)(F)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)C(F)(F)F)cc2)nc1

Procedure:
The title compound was prepared essentially as in Example 1 by combining 5-octyl-2-(4-hydroxyphenyl)pyrimidine (1.01 g, 3.56 mmol) and 4-(6-(2-(nonafluorobutoxy)tetrafluoroethoxy)-2,2,3,3,4,4,5,5,6,6-decafluorohexyloxy)-1-bromobutane (3.07 g, 4.0 mmol; prepared by combining 1,4-dibromobutane and 2-(2-(nonafluorobutoxy)tetrafluoroethoxy)-2,2,3,3,4,4,5,5,6,6-decafluorohexanol). The resulting crude product was isolated and further purified essentially as described in Example 3, eluting with 15 volume percent ethyl acetate/hexane, to yield 2.3 g of purified product.