Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:34]([C:37]1[CH:38]=[N:39][C:40]2[C:45]([C:46]=1[NH:47][C:48]1[CH:53]=[CH:52][CH:51]=[C:50]([O:54][CH3:55])[CH:49]=1)=[CH:44][C:43]([S:56]([C:59]1[CH:60]=[C:61]([CH:65]=[CH:66][CH:67]=1)[C:62]([OH:64])=O)(=[O:58])=[O:57])=[CH:42][C:41]=2[CH3:68])(=[O:36])[NH2:35].O1[C:73]2([CH2:78][CH2:77][NH:76][CH2:75][CH2:74]2)[O:72]CC1.Cl>CN(C=O)C.C1COCC1.CCOC(C)=O.O>[CH3:55][O:54][C:50]1[CH:49]=[C:48]([NH:47][C:46]2[C:45]3[C:40](=[C:41]([CH3:68])[CH:42]=[C:43]([S:56]([C:59]4[CH:67]=[CH:66][CH:65]=[C:61]([C:62]([N:76]5[CH2:77][CH2:78][C:73](=[O:72])[CH2:74][CH2:75]5)=[O:64])[CH:60]=4)(=[O:57])=[O:58])[CH:44]=3)[N:39]=[CH:38][C:37]=2[C:34]([NH2:35])=[O:36])[CH:53]=[CH:52][CH:51]=1
Reactant: COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)O)c4)cc23)c1
Reactant: C1CC2(CCN1)OCCO2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CCOC(C)=O
Product: COc1cccc(Nc2c(C(N)=O)cnc3c(C)cc(S(=O)(=O)c4cccc(C(=O)N5CCC(=O)CC5)c4)cc23)c1
Temperature: 50 °C
Reaction time: 0.08 h
Yield: 103.3 %

Procedure:
HATU (348 mg, 0.915 mmol) and DIEA (0.319 mL, 1.83 mmol) were added to a stirring solution of 3-[[3-carbamoyl-4-[(3-methoxyphenyl)amino]-8-methylquinolin-6-yl]sulfonyl]benzoic acid (300 mg, 0.61 mmol) in DMF (6 mL) at rt. After 5 min. 1,4-dioxa-8-azaspiro[4.5]decane (0.156 mL, 1.22 mmol) was added and the resulting solution was stirred for an additional 1.5 h. The reaction mixture was poured into H2O (50 mL) and filtered. The filter cake was washed with H2O then dried to give a yellow solid. To the solid dissolved in THF (6 mL) was added 5 N HCl (1.22 mL, 6.1 mmol). The reaction mixture was heated to 50° C. and stirred over night. The resulting mixture was cooled to rt, and diluted with EtOAc (20 mL). The organic layer was washed with said. NaHCO3 (20 mL), H2O (20 mL), brine (20 mL), dried over Na2SO4 (s), then concentrated to give the title compound (361 mg) as a yellow solid. The compound was used with no further purification. ES/MS calcd. for C30H29N4O6S+ 573.2. Found m/z=573.2 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[CH2:6][NH2:7].[CH3:13][O:14][C:15](=[O:34])[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:23]=[C:24](Cl)[C:25]3[C:30]([Cl:31])=[C:29]([CH3:32])[S:28][C:26]=3[N:27]=2)=[CH:18][CH:17]=1>>[CH3:13][O:14][C:15](=[O:34])[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[N:23]=[C:24]([NH:7][CH2:6][C:5]3[CH:8]=[CH:9][C:10]([O:11][CH3:12])=[C:3]([O:2][CH3:1])[CH:4]=3)[C:25]3[C:30]([Cl:31])=[C:29]([CH3:32])[S:28][C:26]=3[N:27]=2)=[CH:18][CH:17]=1
Reactant: COc1ccc(CN)cc1OC
Reactant: COC(=O)c1ccc(-c2nc(Cl)c3c(Cl)c(C)sc3n2)cc1
Product: COC(=O)c1ccc(-c2nc(NCc3ccc(OC)c(OC)c3)c3c(Cl)c(C)sc3n2)cc1

Procedure:
The reaction procedure as above wherein 3,4-dimethoxy-benzylamine is reacted with 4-(4-chloro-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidin-2-yl)-benzoic acid methylester yields 4-[4-(3,4-dimethoxybenzylamino)-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidin-2-yl]-benzoic acid methylester
Reaction SMILES: [NH:1]([C:8]1[CH:9]=[C:10]2[C:15](=[O:16])[NH:14][C:12](=[O:13])[C:11]2=[CH:17][C:18]=1[NH:19][C:20]1[CH:25]=[C:24]([O:26]C)[C:23]([O:28]C)=[C:22]([O:30]C)[CH:21]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br>ClCCl>[NH:1]([C:8]1[CH:9]=[C:10]2[C:15](=[O:16])[NH:14][C:12](=[O:13])[C:11]2=[CH:17][C:18]=1[NH:19][C:20]1[CH:25]=[C:24]([OH:26])[C:23]([OH:28])=[C:22]([OH:30])[CH:21]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1cc(Nc2cc3c(cc2Nc2ccccc2)C(=O)NC3=O)cc(OC)c1OC
Agent: BrB(Br)Br
Solvent: ClCCl
Product: O=C1NC(=O)c2cc(Nc3cc(O)c(O)c(O)c3)c(Nc3ccccc3)cc21
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a suspension of 78 mg (0.18 mmol) of 4-anilino-5-(3,4,5-trimethoxy-anilino)phthalimide (Example 27) in 4 ml of dichloromethane, a solution of 314 μl (3.24 mmol) boron tribromide is added dropwise at RT. The reaction mixture is stirred for 4 hours at RT, is then cooled to 0° and quenched with 5 ml of water, and the phases are separated. The water phase is extracted three times with ethyl acetate. The organic phases are combined and washed twice with water, dried over magnesium sulfate and concentrated by evaporation. Excluding light, the evaporation residue is chromatographed with ethylacetate/dichloromethane 4:1 on a silica gel column (precoated with 0.4 g of sodium ascorbate per g silica gel) that is cooled with ice-water (double jacket), the product fractions are combined and concentrated by evaporation yielding the title compound in the form of dark red crystals, m.p. 152° C. (decomp.), FAB-MS: 378 [M+ +H].
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=2)=[O:9])[CH:5]=[CH:4][CH:3]=1.[N:22]1[CH:27]=[C:26](B(O)O)[CH:25]=[N:24][CH:23]=1>>[N:22]1[CH:27]=[C:26]([C:2]2[N:7]=[C:6]([C:8]([NH:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=3)=[O:9])[CH:5]=[CH:4][CH:3]=2)[CH:25]=[N:24][CH:23]=1
Reactant: O=C(Nc1ccc(OC(F)(F)F)cc1)c1cccc(Br)n1
Reactant: OB(O)c1cncnc1
Product: O=C(Nc1ccc(OC(F)(F)F)cc1)c1cccc(-c2cncnc2)n1

Procedure:
The title compound was prepared in an analogous fashion to that described in Example 57 using 6-bromo-N-(4-(trifluoromethoxy)phenyl)picolinamide (Stage 73.1) and 5-pyrimidine boronic acid to afford the title compound as a white powder. UPLC-MS (Condition 2) tR=1.08 min, m/z=361.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.43 (d, J=9.38 Hz, 2H) 8.02 (m, J=9.00 Hz, 2H) 8.20-8.28 (m, 2H) 8.42-8.47 (m, 1H) 9.33 (s, 1H) 9.81 (s, 2H) 10.76 (s, 1H).
Reaction SMILES: Br[CH2:2][C@@H:3]([NH2:10])[CH2:4][C:5]1[NH:6][CH:7]=[N:8][CH:9]=1.C([O-])(=O)C.[Na+]>C(O)(=O)C.[Pd]>[N:8]1[CH:9]=[C:5]([CH2:4][C@H:3]([NH2:10])[CH3:2])[NH:6][CH:7]=1
Reactant: N[C@H](CBr)Cc1cnc[nH]1
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: C[C@@H](N)Cc1cnc[nH]1
Temperature: 25 °C
Reaction time: 60 h

Procedure:
1.5 g (S)-1-bromomethyl-2-(3H-imidazol-4-yl)-ethylamine and 1.87 g sodium acetate are dissolved in 94 mL acetic acid (10%). After the addition of 400 mg palladium/C the suspension is shaken under 3.5 bar H2 pressure at RT for about 60 h. After the catalyst has been filtered off the solvent is eliminated in vacuo and the crude product is used without further purification in the following reaction step.
Reaction SMILES: [CH2:1]([N:4]([CH2:17][C:18]([O:20]CC)=[O:19])[NH:5][C:6](=[O:16])[NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:9])[CH:2]=[CH2:3].O.[OH-].[Li+]>>[CH2:1]([N:4]([CH2:17][C:18]([OH:20])=[O:19])[NH:5][C:6](=[O:16])[NH:7][C@@H:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:9])[CH:2]=[CH2:3]
Reactant: C=CCN(CC(=O)OCC)NC(=O)N[C@H](C)c1ccccc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Product: C=CCN(CC(=O)O)NC(=O)N[C@H](C)c1ccccc1
Reaction time: 2 h
Yield: 97.1 %

Procedure:
According to the procedure described in the synthesis method of Compound VI-2 with the modification that the reaction was carried out for 2 hours, (R)-ethyl 2-(1-allyl-2-(1-phenylethylcarbamoyl)hydrazinyl)acetate (Compound V-3) 229 mg (0.75 mmol) was reacted with lithium hydroxide monohydrate 38 mg (0.9 mmol) to obtain the title compound 202 mg (97%).
Reaction SMILES: [C:1]1([C:7]2[O:11][C:10]([C:12]([N:14]3[CH2:17][CH:16]([O:18][C:19]4[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=4)[CH2:15]3)=[O:13])=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH2:28]1[C:31]2([CH2:35][CH2:34][O:33][CH2:32]2)[CH2:30][NH:29]1.C(N(CC)CC)C.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:28]1[C:31]2([CH2:35][CH2:34][O:33][CH2:32]2)[CH2:30][N:29]1[CH2:23][C:22]1[CH:21]=[CH:20][C:19]([O:18][CH:16]2[CH2:15][N:14]([C:12]([C:10]3[O:11][C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)=[N:8][N:9]=3)=[O:13])[CH2:17]2)=[CH:26][CH:25]=1
Reactant: C1CC2(CNC2)CO1
Reactant: O=Cc1ccc(OC2CN(C(=O)c3nnc(-c4ccccc4)o3)C2)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(c1nnc(-c2ccccc2)o1)N1CC(Oc2ccc(CN3CC4(CCOC4)C3)cc2)C1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 4-(1-(5-phenyl-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (70 mg, 0.20 mmol) in dichloromethane (2 mL) was added 6-oxa-2-azaspiro[3.4]octane hydrochloride (56 mg, 0.37 mmol) and triethylamine (0.100 mL, 0.72 mmol). After stirring at ambient temperature for 30 minutes, sodium triacetoxyhydroborate (95 mg, 0.45 mmol) was added. Stirring was continued at ambient temperature overnight, after which NaHCO3 (aq, sat, 5 ml) was added. The phases were separated with the aid of a phase separator. The aqueous phase was extracted twice with dichloromethane and dried using a phase separator. The combined organic phases were concentrated in vacuo to afford a colourless residue weighing 92 mg.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[F:15].C(=O)(O)[O-].[Na+].[C:21](Cl)(Cl)=[S:22]>CC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:21]=[S:22])=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[F:15]
Reactant: S=C(Cl)Cl
Reactant: Nc1ccc(Cl)c(-c2ccncc2F)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Product: Fc1cnccc1-c1cc(N=C=S)ccc1Cl
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
The mixture containing 4-chloro-3-(3-fluoropyridin-4-yl)benzenamine (1 eq) and sodium bicarbonate (2 eq) in acetone was treated with thiophosgene (2 eq) and stirred for 5 minutes at 0° C. Reaction then concentrated and partitioned between ethyl acetate and water. Organic layer dried over sodium sulfate and sodium bicarbonate and concentrated to give 4-(2-chloro-5-isothiocyanatophenyl)-3-fluoropyridine. HPLC=5.54 min; MS: MH+=265.
Reaction SMILES: [NH2:1][C@@:2]1([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])[CH2:7][O:6][C@@H:5]([CH2:8][O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:4][C@H:3]1[CH2:17][OH:18].FC1C=C(F)C=CC=1[C@@]1(N[C:44]([NH:46][C:47](=[O:63])[O:48][CH2:49][CH:50]2[C:62]3[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=3[C:56]3[C:51]2=[CH:52][CH:53]=[CH:54][CH:55]=3)=[S:45])[C@H](CO)CCOC1>>[CH2:10]([O:9][CH2:8][C@@H:5]1[O:6][CH2:7][C@@:2]([NH:1][C:44]([NH:46][C:47](=[O:63])[O:48][CH2:49][CH:50]2[C:51]3[CH:52]=[CH:53][CH:54]=[CH:55][C:56]=3[C:57]3[C:62]2=[CH:61][CH:60]=[CH:59][CH:58]=3)=[S:45])([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])[C@H:3]([CH2:17][OH:18])[CH2:4]1)[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: N[C@@]1(c2ccc(F)cc2F)CO[C@@H](COCc2ccccc2)C[C@H]1CO
Reactant: O=C(NC(=S)N[C@@]1(c2ccc(F)cc2F)COCC[C@H]1CO)OCC1c2ccccc2-c2ccccc21
Product: O=C(NC(=S)N[C@@]1(c2ccc(F)cc2F)CO[C@@H](COCc2ccccc2)C[C@H]1CO)OCC1c2ccccc2-c2ccccc21

Procedure:
Conversion of [(2R,4R,5S)-5-amino-2-[(benzyloxy)methyl]-5-(2,4-difluorophenyl)tetrahydro-2H-pyran-4-yl]methanol (C22) to the product was carried out according to the general procedure for the synthesis of 9H-fluoren-9-ylmethyl {[(3S,4R)-3-(2,4-difluorophenyl)-4-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]carbamothioyl}carbamate (C12) in Example 1. The product was obtained as a white solid. Yield: 995 mg, 1.54 mmol, 75%. LCMS m/z 645.6 (M+1). 1H NMR (400 MHz, CDCl3), characteristic peaks: δ 3.52 (dd, J=10.3, 4.1 Hz, 1H), 3.64 (dd, J=10.2, 6.0 Hz, 1H), 4.46 (dd, half of ABX pattern, J=10.6, 6.9 Hz, 1H), 4.60 (AB quartet, JAB=12.0 Hz, ΔνAB=11.1 Hz, 2H), 6.73-6.81 (m, 1H), 6.86-6.92 (m, 1H), 7.20-7.25 (m, 1H), 7.42-7.48 (m, 2H), 7.54-7.59 (m, 2H).
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[CH2:8][CH2:7][CH2:6][C:5](=[CH2:9])[C@H:4]([CH2:10][CH2:11][C:12](=[O:14])[CH3:13])[C@@H:3]1[CH:15]=[O:16]>C1(C)C=CC=CC=1>[OH:16][CH2:15][C@@H:3]1[C:2]([CH3:17])([CH3:1])[CH2:8][CH2:7][CH2:6][C:5](=[CH2:9])[C@@H:4]1[CH2:10][CH2:11][C:12](=[O:14])[CH3:13]
Reactant: C=C1CCCC(C)(C)[C@@H](C=O)[C@H]1CCC(C)=O
Solvent: Cc1ccccc1
Product: C=C1CCCC(C)(C)[C@@H](CO)[C@H]1CCC(C)=O
Temperature: 90 °C

Procedure:
(1S,7R)-2,2-dimethyl-6-methylene-7-(3-oxobutyl)cycloheptanecarbaldehyde (11.8 g, 0.05 mol.), toluene (70.8 g, 600 wt. %) and (ethylenediamine)[1,2-bis(diphenylphosphino) ethane]ruthenium(bispivalate) (4.8 mg, 0.00625 mmol, 0.0125 mol.%) were loaded altogether in a 200 ml autoclave equipped with a mechanical stirring device. Sealed autoclave was then purged under stirring with nitrogen (3 times 5 bars) and hydrogen (3 times 5 bars) before being pressurized to 50 bars hydrogen. It was then heated to 90° C. and hydrogen pressure was maintained to 30 bars during all the reaction to afford desired product with 92% selectivity. Upon reaction completion (checked by both hydrogen consumption and GC), autoclave was then cooled down to 25° C. It was then depressurized and purged with nitrogen (3 times 5 bars) and reaction mixture was then transferred to a round-bottomed flask and solvent was removed under vacuum. After flash chromatography, 4-((1R,2S)-2-(hydroxymethyl)-3,3-dimethyl-7-methylenecycloheptyl) butan-2-one was obtained in 85% yield.
Reaction SMILES: C[O:2][C:3]([C:5]1[S:6][C:7]([C:11](=[O:28])[NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][Si](C(C)(C)C)(C)C)[CH:15]=2)=[CH:8][C:9]=1[Cl:10])=[O:4].O.[OH-].[Li+].C1COCC1.Cl>O>[Cl:10][C:9]1[CH:8]=[C:7]([C:11](=[O:28])[NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([OH:20])[CH:15]=2)[S:6][C:5]=1[C:3]([OH:4])=[O:2]
Reactant: COC(=O)c1sc(C(=O)NCc2cccc(O[Si](C)(C)C(C)(C)C)c2)cc1Cl
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(NCc1cccc(O)c1)c1cc(Cl)c(C(=O)O)s1
Reaction time: 15 h

Procedure:
A mixture of 5-[3-(tert-Butyl-dimethyl-silanyloxy)-benzylcarbamoyl]-3-chloro-thiophene-2-carboxylic acid methyl ester (260 mg, 0.59 mmol), lithium hydroxide monohydrate (500, mg, 11.82 mmol), THF (5 mL) and water (5 mL) was stirred 15 h, acidified with 1N HCl and extracted with EtOAc (×3). The organic extracts were combined, washed with brine, dried over sodium sulfate, filtered and evaporated to give the title compound, 230 mg (100%). MS m/e 311.9 (M+H+).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[CH:11]1[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:15]([CH3:22])[NH:14][C:13](=[O:23])[NH:12]1>C(OC(=O)C)(=O)C>[C:2]([N:12]1[CH:11]([C:3]2[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=2[O:1][C:17](=[O:18])[CH3:16])[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:15]([CH3:22])[NH:14][C:13]1=[O:23])(=[O:1])[CH3:3]
Reactant: CCOC(=O)C1=C(C)NC(=O)NC1c1cc([N+](=O)[O-])ccc1O
Solvent: CC(=O)OC(C)=O
Product: CCOC(=O)C1=C(C)NC(=O)N(C(C)=O)C1c1cc([N+](=O)[O-])ccc1OC(C)=O

Procedure:
A suspension of ethyl 1,2,3,4-tetrahydro-4-(2-hydroxy-5-nitrophenyl)-6-methyl-2-oxo-5-pyrimidine carboxylate (1.00 g, 31.0 mmol) in acetic anhydride (25 mL) was heated to reflux for 2 hours. The reaction mixture was cooled and the excess acetic anhydride was removed in vacuo to afford the desired product as a tan solid which was used in the next reaction without purification.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:10]1[CH:14]=[CH:13][N:12]=[CH:11]1>>[C:1]([C:11]1[NH:10][CH:14]=[CH:13][N:12]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: c1c[nH]cn1
Reactant: O=C(Cl)c1ccccc1
Product: O=C(c1ccccc1)c1ncc[nH]1
Yield: 71 %

Procedure:
Benzoyl imidazole was prepared by the above procedure using benzoyl chloride (28.1 grams, 200 mmole) and imidazole (14.3 grams, 210 mmole), in an amount of 24.3 grams (71% yield).
Reaction SMILES: [C:1](Cl)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[CH:8]1[CH:9]=[C:10]([N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH2:24][CH2:25][O:26][C:27]3[CH:28]=[CH:29][C:30]4[CH2:37][CH2:36][C:34](=[O:35])[NH:33][C:31]=4[CH:32]=3)[CH2:18][CH2:17]2)[C:11]([Cl:15])=[C:12]([Cl:14])[CH:13]=1>N1C=CC=CC=1.C1C=C(N2CCN(CCCCOC3C=CC4CCC(=O)NC=4C=3)CC2)C(Cl)=C(Cl)C=1>[C:1]([O:35][C:34]1[CH2:36][CH2:37][C:30]2[C:31](=[CH:32][C:27]([O:26][CH2:25][CH2:24][CH2:23][CH2:22][N:19]3[CH2:20][CH2:21][N:16]([C:10]4[CH:9]=[CH:8][CH:13]=[C:12]([Cl:14])[C:11]=4[Cl:15])[CH2:17][CH2:18]3)=[CH:28][CH:29]=2)[N:33]=1)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3]
Reactant: CC(C)(C)C(=O)Cl
Reactant: O=C1CCc2ccc(OCCCCN3CCN(c4cccc(Cl)c4Cl)CC3)cc2N1
Solvent: c1ccncc1
Product: CC(C)(C)C(=O)OC1=Nc2cc(OCCCCN3CCN(c4cccc(Cl)c4Cl)CC3)ccc2CC1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 501.1 %

Procedure:
To a stirred solution of aripiprazole (0.1 g, 0.223 mmol) in pyridine (1 mL) at 0° C. was added pivaloyl chloride (0.055 mL, 0.446 mmol). After stirring at 0° C. for 5 minutes the reaction was allowed to warm to room temperature. After a further 5 minutes the temperature was increased to 50° C. for approximately 19 hours. The reaction was allowed to cool to room temperature. The reaction was repeated in a similar manner using of aripiprazole (1.75 g, 3.90 mmol). The two reaction mixtures were combined and quenched with approximately methanol (5 mL). The majority of the pyridine was removed in vacuo and the residue partitioned between dichloromethane (30 mL) and saturated NaHCO3 solution (30 mL). The aqueous phase was extracted with dichloromethane (2×30 mL) and the combined organic extracts washed with brine (20 mL) and dried over MgSO4. After filtration, the volatiles were removed (toluene and methanol/dichloromethane azeotrope) and the residue purified by silica chromatography eluting first with dichloromethane followed by ethyl acetate/dichloromethane/methanol (1:1:0.04) to give the title compound (1.19 g, 54%).
Reaction SMILES: C([O-])(O)=O.C([O-])(O)=O.C([O-])(O)=O.C([O-])(O)=O.[Zr+4:17].C(=O)=O.[P:21](=[O:25])([OH:24])([OH:23])[OH:22].[OH-].[K+]>O.[Hf]>[P:21]([O-:25])([O-:24])([O-:23])=[O:22].[Zr+4:17].[P:21]([O-:25])([O-:24])([O-:23])=[O:22].[P:21]([O-:25])([O-:24])([O-:23])=[O:22].[P:21]([O-:25])([O-:24])([O-:23])=[O:22].[Zr+4:17].[Zr+4:17]
Reactant: O=P(O)(O)O
Agent: [Hf]
Agent: [Zr+4]
Agent: O=C([O-])O
Solvent: O
Product: O=P([O-])([O-])[O-]
Reaction time: 2 h

Procedure:
0.67 moles of zirconium basic carbonate (3ZrO2.CO2.xH2O) containing 2.1% hafnium composed of particles wherein a median particle size thereof was 18 μm and particles with a particle size of 0.8 μm to 50 μm were present at 100% on a volume basis of the total particles were suspended in 300 ml of deionized water, and 0.27 moles of phosphoric acid were added thereto with stirring. A 20% aqueous solution containing 0.07 moles of potassium hydroxide was further added thereto, followed by heating and aging for 2 hours at 98° C. Then, the resulting solid was sufficiently washed with deionized water in a ceramic filter washing machine until an electric conductivity of the filtrate reached 300 μS or less and the solid was taken out and dried at 120° C. for 3 hours.
Reaction SMILES: [CH2:1]([C@:3]1([OH:28])[C:25]2[CH:24]=[C:23]3[N:10]([CH2:11][C:12]4[C:13]3=[N:14][C:15]3[CH:16]=[C:17]([F:22])[CH:18]=[CH:19][C:20]=3[CH:21]=4)[C:9](=[O:26])[C:8]=2[CH2:7][O:6][C:5](=[O:27])[CH2:4]1)[CH3:2].[CH3:29][CH:30]([CH3:35])[CH2:31][CH2:32]C=O>>[CH2:1]([C@:3]1([OH:28])[C:25]2[CH:24]=[C:23]3[N:10]([CH2:11][C:12]4[C:13]3=[N:14][C:15]3[CH:16]=[C:17]([F:22])[CH:18]=[CH:19][C:20]=3[C:21]=4[CH2:32][CH2:31][CH:30]([CH3:35])[CH3:29])[C:9](=[O:26])[C:8]=2[CH2:7][O:6][C:5](=[O:27])[CH2:4]1)[CH3:2]
Reactant: CC(C)CCC=O
Reactant: CC[C@@]1(O)CC(=O)OCc2c1cc1n(c2=O)Cc2cc3ccc(F)cc3nc2-1
Product: CC[C@@]1(O)CC(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1cc(F)ccc1c2CCC(C)C

Procedure:
The product of Example 2 is treated with 4-methylpentanal according to a procedure similar to Stage 13e in order to produce the expected solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10].[Cl:12][C:13]1[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:14]=1[NH2:15]>>[Cl:12][C:13]1[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][C:14]=1[NH:15][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=[O:10]
Reactant: Cc1cccc(N)c1Cl
Reactant: O=C(O)Cc1ccccc1Br
Product: Cc1cccc(Nc2ccccc2CC(=O)O)c1Cl

Procedure:
In the manner described in example 3, 2-bromophenylacetic acid is condensed with 2-chloro-3-methylaniline to yield 2-[(2-chloro-3-methylphenyl)amino]phenylacetic acid.
Reaction SMILES: [K].N#N.C(=[C:7]([CH:9]([CH2:11][OH:12])[OH:10])[OH:8])(C)C.CS(O[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])(=O)=O>C1C=CC=CC=1>[CH2:33]([O:12][CH2:11][CH:9]([CH2:7][OH:8])[OH:10])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH3:18]
Reactant: CCCCCCCCCCCCCCCCOS(C)(=O)=O
Reactant: CC(C)=C(O)C(O)CO
Agent: N#N
Agent: [K]
Solvent: c1ccccc1
Product: CCCCCCCCCCCCCCCCOCC(O)CO
Yield: 74.9 %

Procedure:
Potassium metal (1.5 g, 38.36 mmol) and anhydrous benzene (180 ml) were placed in a 500 ml three-neck round-bottomed flask equipped with a reflux condenser, dropping funnel, stir bar, and N2 atmosphere. The reaction mixture was refluxed. When the potassium metal had melted, isopropylidene glycerol (6 ml, 48.25 mmol) was added dropwise and the reaction continued to reflux an additional 2.5 hours. A solution of hexadecyl methane sulfonate (10.0 g, 32.25 mmol) in anhydrous benzene (80 ml) was added dropwise and the reaction refluxed overnight. The heat was removed and the reaction mixture was coled to 0° C. Water was added and the benzene layer was removed, washed with H2O, dried (MgSO4) and filtered. This residue was treated as in METHOD A for the hydrolysis of the acetal group to provide compound 35, rac-1-O-hexadecylglycerol (7.65 g, 75%, based on mesylate 34).
Reaction SMILES: C[O:2][C:3](=[O:27])[CH2:4][CH2:5][CH2:6][N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:16][CH:15]=1.[OH-].[Na+]>CO.O>[CH2:20]([C:17]1[CH:18]=[CH:19][C:14]([O:13][CH2:12][C@@H:8]2[CH2:9][CH2:10][CH2:11][N:7]2[CH2:6][CH2:5][CH2:4][C:3]([OH:27])=[O:2])=[CH:15][CH:16]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: COC(=O)CCCN1CCC[C@H]1COc1ccc(Cc2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)CCCN1CCC[C@H]1COc1ccc(Cc2ccccc2)cc1
Temperature: 50 °C
Reaction time: 67 h
Yield: 72.8 %

Procedure:
To a solution of the product from step 1 (0.13 g, 0.35 mmol) was added 2N NaOH (0.29 mL, 0.58 mmol) and 80% MeOH/H2O (4 mL). The resulting slurry was stirred at 50° C. for 67 h. The solvent was removed under reduced pressure and water was added to the residue. The pH was adjusted to 4 using 1 N HCl solution. The crude product was extracted with ethyl acetate. The combined organic layers were washed with water, washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to afford the title compound (0.09 g, 77%) as a yellow semi-solid. 1H NMR (400 MHz, CDCl3); δ 1.96-2.26 (m, 6H), 2.41 (t, J=6.6 Hz, 2H), 3.02 (m, 2H), 3.47 (m, 1H), 3.67 (m, 2H), 3.89 (s, 2H), 3.85 (dd, J1=4.0 Hz, J2=10.8 Hz, 1H), 4.50 (m, 1H), 6.84 (d, J=8.8 Hz, 2H), 7.09-7.19 (m, 5H), 7.25-7.28 (m, 2H); MS (m/z) 352.4 (M−1); LC (97.6%); HPLC (96.6%).