Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=O)=[CH:8][CH:7]=2)=[CH:2]1.Cl.[F:17][C:18]([F:30])([F:29])[CH:19]([C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][N:22]=1)[NH2:20].C(N(CC)CC)C.C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C>[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[CH:8][C:9]([CH2:12][C:13]([NH:20][C@@H:19]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][N:22]=3)[C:18]([F:29])([F:17])[F:30])=[O:15])=[CH:10][CH:11]=2)=[CH:2]1
Reactant: COc1ccc(C(N)C(F)(F)F)nc1
Reactant: O=C(O)Cc1ccc(-c2ccsc2)cc1
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: ClCCCl
Product: COc1ccc([C@H](NC(=O)Cc2ccc(-c3ccsc3)cc2)C(F)(F)F)nc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 0.04 g (0.18 mmol) [4-(3-thienyl)phenyl]acetic acid in 0.75 mL DMF was added 0.06 g (0.2 mmol) 2,2,2-trifluoro-1-(5-methoxypyridin-2-yl)ethanamine hydrochloride, 0.1 mL (0.6 mmol) triethylamine, 0.03 g (0.2 mmol) HOAt, and 0.05 g (0.2 mmol) EDC and the mixture stirred for 1 hour at room temperature. Purification (no workup) by preparative reverse phase HPLC (linear gradient 5 to 95% CH3CN/H2O over 30 min, 0.05% added TFA, C18 SunFire 19×150 mm) afforded 2-[4-(3-thienyl)phenyl]-N-[(1S)-2,2,2-trifluoro-1-(5-methoxypyridin-2-yl)ethyl]acetamide high resolution mass spec calc for C20H17F3N2O2S 407.1036, found 407.1043.
Reaction SMILES: Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[N:7]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][N:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)=[C:14]([F:26])[CH:13]=3)[CH:6]=[N:5][C:4]=2[CH:3]=1.[NH:27]1[CH2:31][CH2:30][CH2:29][C:28]1=[O:32]>>[F:26][C:14]1[CH:13]=[C:12]([N:7]2[C:8](=[O:11])[C:9]3[S:10][C:2]([N:27]4[CH2:31][CH2:30][CH2:29][C:28]4=[O:32])=[CH:3][C:4]=3[N:5]=[CH:6]2)[CH:17]=[CH:16][C:15]=1[O:18][CH2:19][CH2:20][N:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: O=c1c2sc(Br)cc2ncn1-c1ccc(OCCN2CCCC2)c(F)c1
Reactant: O=C1CCCN1
Product: O=C1CCCN1c1cc2ncn(-c3ccc(OCCN4CCCC4)c(F)c3)c(=O)c2s1

Procedure:
6-Bromo-3-[3-fluoro-4-(2-pyrrolidin-1-ylethoxy)phenyl]-3H-thieno[3,2-d]pyrimidin-4-one was reacted with 2-pyrrolidone by method S. The product with the molecular weight of 442.52 (C22H23FN4O3S) was obtained in this way; MS (ESI): 443 (M+H+).
Reaction SMILES: [CH2:1]([NH:3][C:4]1[C:13]([CH:14]=[O:15])=[CH:12][C:11]2[C:6](=[CH:7][C:8]([F:18])=[C:9]([O:16][CH3:17])[CH:10]=2)[N:5]=1)[CH3:2].[BH4-].[Na+]>C1COCC1>[CH2:1]([NH:3][C:4]1[C:13]([CH2:14][OH:15])=[CH:12][C:11]2[C:6](=[CH:7][C:8]([F:18])=[C:9]([O:16][CH3:17])[CH:10]=2)[N:5]=1)[CH3:2]
Reactant: CCNc1nc2cc(F)c(OC)cc2cc1C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCNc1nc2cc(F)c(OC)cc2cc1CO
Temperature: 25 °C
Reaction time: 8 h
Yield: 58 %

Procedure:
To a solution of 2-(ethylamino)-7-fluoro-6-methoxyquinoline-3-carbaldehyde CCH 42068 (500 mg, 2.01 mmol) in THF (50 mL) in a 100 mL round-bottomed flask equipped with a magnetic stirrer was added NaBH4 (80 mg, 2.11 mmol) and the reaction mixture was stirred overnight at RT, then cooled in an ice bath and quenched by addition of a 6 N aqueous HCl solution (10 mL). The mixture was then basified with a 10 N aqueous NaOH solution (to pH=12). THF was then removed at 40° C. under vacuum and the residue was taken up in CH2Cl2 (50 mL) and the organic phase was isolated, washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 50:50) followed by a new purification by column chromatography (SiO2, eluent CH2Cl2:EtOAc=100:0 to 90:10) gave (2-ethylamino-7-fluoro-6-methoxyquinolin-3-yl)methanol SMA 44090 as a white solid (290 mg, 58% yield).
Reaction SMILES: O=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13].Br[C:17](Br)([F:19])[F:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CC(N(C)C)=O.O.[Zn]>[F:18][C:17]([F:19])=[CH:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]
Reactant: FC(F)(Br)Br
Reactant: COC(=O)CCCCCCCCCC=O
Agent: [Zn]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC(=O)N(C)C
Solvent: O
Product: COC(=O)CCCCCCCCCC=C(F)F
Temperature: 25 °C
Reaction time: 60 h
Yield: 49.5 %

Procedure:
A stirred mixture of 7.5 grams (0.035 mole) of methyl 11-oxoundecanoate and 14.7 grams (0.07 mole) of dibromodifluoromethane was cooled to 0°-10° C., and a solution of 18.4 grams (0.07 mole) of triphenylphosphine in 50 ml of dimethylacetamide was added dropwise. During the addition the temperature of the reaction mixture was maintained at 0°-10° C. Upon completion of addition the reaction mixture was allowed to warm to ambient temperature, and 4.6 grams (0.07 mole) of zinc dust was added in two portions. The addition caused an exothermic reaction which raised the temperature of the reaction mixture to 90° C. The reaction mixture was allowed to cool to ambient temperature where it stood without stirring for 60 hours. The reaction mixture was diluted with water and was subjected to a steam distillation with pentane. The appropriate fractions were combined and concentrated under reduced pressure yielding 4.3 grams of methyl 12,12-difluoro-11-dodecenoate. The nmr spectrum was consistent with the proposed structure.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[CH2:9][CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6][C:5]=2[C:4]([CH3:18])=[N:3]1.[ClH:19]>CO.CCOC(C)=O>[ClH:19].[CH3:1][N:2]1[C:10]2[CH2:9][CH2:8][NH:7][CH2:6][C:5]=2[C:4]([CH3:18])=[N:3]1
Reactant: Cc1nn(C)c2c1CN(C(=O)OC(C)(C)C)CC2
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CO
Product: Cc1nn(C)c2c1CNCC2
Yield: 90.9 %

Procedure:
To a solution of tert-butyl 1,3-dimethyl-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate (3.00 g) in MeOH was added a solution of HCl in EtOAc (3.0 M). White solid was precipitated out after 3.0 h reaction. The resulted mixture was filtered and the residue was dried to give the title compound as a white solid (2.00 g, 90.90%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 152.21 (M+1).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:3]=1.[C:15]([S:19]([NH:22][C@@H:23]1[CH2:28][CH2:27][C@H:26]([C:29](O)=O)[CH2:25][CH2:24]1)(=[O:21])=[O:20])([CH3:18])([CH3:17])[CH3:16]>>[C:15]([S:19]([NH:22][C@@H:23]1[CH2:24][CH2:25][C@H:26]([C:29]2[NH:8][C:7]3[C:2](=[N:3][C:4]([C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)=[N:5][CH:6]=3)[N:1]=2)[CH2:27][CH2:28]1)(=[O:21])=[O:20])([CH3:18])([CH3:16])[CH3:17]
Reactant: CC(C)(C)S(=O)(=O)N[C@H]1CC[C@@H](C(=O)O)CC1
Reactant: Nc1cnc(-c2ccccc2)nc1N
Product: CC(C)(C)S(=O)(=O)N[C@H]1CC[C@@H](c2nc3nc(-c4ccccc4)ncc3[nH]2)CC1

Procedure:
By following the same procedure as described in Example 1 except that use was made of 4,5-diamino-2-phenylpyrimidine and cis-4-tert-butylsulfonylaminocyclohexanecarboxylic acid in place of 4-trifluoromethyl-1,2-phenylenediamine, the title compound was prepared.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10](=[O:34])[NH:11][C:12]1[CH:13]=[C:14]([N:18]2[C:23](=[O:24])[C:22]([CH2:25][CH2:26][C:27]([OH:29])=[O:28])=[N:21][C:20]3[CH:30]=[CH:31][CH:32]=[N:33][C:19]2=3)[CH:15]=[CH:16][CH:17]=1.O[N:36]1[C:40](=[O:41])[CH2:39][CH2:38][C:37]1=[O:42].C(N=C=NCCCN(C)C)C>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9][C:10](=[O:34])[NH:11][C:12]1[CH:13]=[C:14]([N:18]2[C:23](=[O:24])[C:22]([CH2:25][CH2:26][C:27]([O:29][N:36]3[C:40](=[O:41])[CH2:39][CH2:38][C:37]3=[O:42])=[O:28])=[N:21][C:20]3[CH:30]=[CH:31][CH:32]=[N:33][C:19]2=3)[CH:15]=[CH:16][CH:17]=1
Reactant: O=C1CCC(=O)N1O
Reactant: COc1ccccc1NC(=O)Nc1cccc(-n2c(=O)c(CCC(=O)O)nc3cccnc32)c1
Agent: CCN=C=NCCCN(C)C
Product: COc1ccccc1NC(=O)Nc1cccc(-n2c(=O)c(CCC(=O)ON3C(=O)CCC3=O)nc3cccnc32)c1
Reaction time: 24 h
Yield: 84.4 %

Procedure:
To a stirred solution of 4-[3-[3-(2-methoxyphenyl)ureido]phenyl]-3-oxo-2-(2-carboxyethyl)-3,4-dihydropyrido[2,3-b]pyrazine (2.30 g) and N-hydroxysuccinimide (1.15 g) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (1.20 g) and the resulting mixture was stirred for 24 hours. The reaction mixture was concentrated, diluted with ethyl acetate, washed with a saturated sodium bicarbonate solution, water and brine, and dried over magnesium sulfate. After evaporation of the solvent, the residue was triturated with ether to give 4-[3-[3-(2-methoxyphenyl)ureido]-phenyl]-3-oxo-2-[2-succinimidooxycarbonylethyl)-3,4-dihydropyrido[2,3-b]pyrazine (2.35 g) as a solid.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([C:18](=[O:22])[C@@H:19]([OH:21])[CH3:20])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.B(O)(O)[C:30]1[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[N:32][CH:31]=1>>[OH:21][C@@H:19]([CH3:20])[C:18]([N:15]1[CH2:16][CH2:17][N:12]([CH2:11][C:9]2[S:10][C:5]3[C:4]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[N:3][C:2]([C:30]4[CH:31]=[N:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=4)=[N:7][C:6]=3[CH:8]=2)[CH2:13][CH2:14]1)=[O:22]
Reactant: C[C@H](O)C(=O)N1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Reactant: COc1ccc(B(O)O)cn1
Product: COc1ccc(-c2nc(N3CCOCC3)c3sc(CN4CCN(C(=O)[C@H](C)O)CC4)cc3n2)cn1
Yield: 55.2 %

Procedure:
(S)-1-(4-((2-Chloro-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one (61 mg) was reacted with 35 mg of 6-methoxypyridin-3-yl-3-boronic acid via General Procedure A to give 39.4 mg of 210. MS (Q1) 499.3 (M)+
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH:13]=[C:14]([C:17]([CH3:20])([CH3:19])[CH3:18])[C:15]=1[OH:16])[CH:8]=[CH:9][C:10](O)=[O:11])([CH3:4])([CH3:3])[CH3:2].Cl.Cl.[N:23]1([CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:33][CH:32]=2)[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.P(Br)(Br)Br.Cl>N1C=CC=CC=1>[C:17]([C:14]1[CH:13]=[C:7]([CH:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:15]=1[OH:16])[CH:8]=[CH:9][C:10]([N:26]1[CH2:27][CH2:28][N:23]([CH2:29][CH2:30][C:31]2[CH:36]=[CH:35][C:34]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:33][CH:32]=2)[CH2:24][CH2:25]1)=[O:11])([CH3:19])([CH3:20])[CH3:18]
Reactant: CC(C)(C)c1cc(C=CC(=O)O)cc(C(C)(C)C)c1O
Reactant: CCOC(=O)Cc1ccc(CCN2CCNCC2)cc1
Agent: BrP(Br)Br
Agent: Cl
Solvent: c1ccncc1
Product: CCOC(=O)Cc1ccc(CCN2CCN(C(=O)C=Cc3cc(C(C)(C)C)c(O)c(C(C)(C)C)c3)CC2)cc1
Reaction time: 2 h

Procedure:
A solution of 14.0 g. (51 mmole) 3,5-di-tert.-butyl-4-hydroxycinnamic acid and 17.7 g. (51 mmole) ethyl 4-[2-(piperazin-1-yl)-ethyl]-phenylacetate dihydrochloride in 150 ml. anhydrous pyridine is mixed dropwise, with ice cooling, with a solution of 3.57 g. (26 mmole) phosphorus tribromide in 20 ml. pyridine. Stirring is continued for 2 hours, with ice cooling, and the reaction mixture then left to stand for 12 hours at ambient temperature, whereafter it is poured on to ice and extracted with ethyl acetate. The extracts are dried and evaporated, the residue is taken up in diethyl ether and the hydrochloride is precipitated with hydrogen chloride-containing diethyl ether. After recrystallisation from a mixture of ethanol and water, to which has been added some concentrated hydrochloric acid, there are obtained 14.5 g. (47%) of hydrochloride of the desired compound; m.p. 111°-113° C.
Reaction SMILES: C([O:3][C:4](=O)[CH:5]([F:13])[C:6]([C:8]1[O:9][CH:10]=[CH:11][CH:12]=1)=O)C.C(=O)(O)O.[NH2:19][C:20]([NH2:22])=[NH:21].Cl>C(O)C.O>[NH2:21][C:20]1[NH:22][C:4](=[O:3])[C:5]([F:13])=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[N:19]=1
Reactant: CCOC(=O)C(F)C(=O)c1ccco1
Reactant: N=C(N)N
Agent: Cl
Agent: O=C(O)O
Solvent: CCO
Solvent: O
Product: Nc1nc(-c2ccco2)c(F)c(=O)[nH]1
Temperature: 100 °C
Yield: 71.8 %

Procedure:
Following the method of Skulnick and Wierenga (Patent WO 86/04583), a mixture of 8.72 g (43.6 mmol) (RS)-2-fluoro-3-furan-2-yl-3-oxo-propionic acid ethyl ester and 8.89 g (49.3 mmol) guanidine carbonate in 30 ml ethanol was heated at 100° C. for 16 hours. The reaction mixture was then cooled to 0° C. and diluted with 100 ml water. 1M hydrochloric acid was added dropwise until the mixture was ca pH 3, whereupon the resulting crystals were collected by filtration and washed sequentially with water and with ether to afford 6.11 g (72%) 2-amino-5-fluoro-6-furan-2-yl-3H-pyrimidin-4-one as a brown crystalline solid. EI-MS m/e (%): 95 (M+, 100), 154 ([M—MeCN]+, 24).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[CH3:14][C:15]1[CH:20]=[C:19]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH:18]=[C:17]([CH3:28])[C:16]=1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35]O)[CH:30]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:28][C:17]1[CH:18]=[C:19]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH:20]=[C:15]([CH3:14])[C:16]=1[C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][O:1][C:2]2[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:7]=2)[CH:30]=1
Reactant: Cc1cc(OC2CCCCO2)cc(C)c1-c1cccc(CO)c1
Reactant: COC(=O)CCc1ccc(O)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)CCc1ccc(OCc2cccc(-c3c(C)cc(OC4CCCCO4)cc3C)c2)cc1
Yield: 37.3 %

Procedure:
To a solution of methyl 3-(4-hydroxyphenyl)propanoate (3.28 g, 18.2 mmol), [2′,6′-dimethyl-4′-(tetrahydro-2H-pyran-2-yloxy)biphenyl-3-yl]methanol (5.15 g, 16.5 mmol) and triphenylphosphine (5.63 g, 21.5 mmol) in tetrahydrofuran (100 mL) was added dropwise diethyl azodicarboxylate (40% toluene solution, 9.7 mL) at 0° C. with stirring, and the mixture was stirred at room temperature for 48 hrs. The reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1-hexane/ethyl acetate=3/1) to give the title compound (2.92 g, yield 37%) as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[N:8]([S:24]([N:27]([CH3:29])[CH3:28])(=[O:26])=[O:25])[C:9]3[C:14]([C:15]=2[C:16]2[CH:21]=[CH:20][C:19]([O:22]C)=[CH:18][CH:17]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:30])[O:4][N:3]=1.B(F)(F)F.S(C)C>C(Cl)Cl.CO>[CH3:1][C:2]1[C:6]([C:7]2[N:8]([S:24]([N:27]([CH3:28])[CH3:29])(=[O:26])=[O:25])[C:9]3[C:14]([C:15]=2[C:16]2[CH:17]=[CH:18][C:19]([OH:22])=[CH:20][CH:21]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3)=[C:5]([CH3:30])[O:4][N:3]=1
Reactant: COc1ccc(-c2c(-c3c(C)noc3C)n(S(=O)(=O)N(C)C)c3ccccc23)cc1
Agent: FB(F)F
Solvent: CSC
Solvent: ClCCl
Solvent: CO
Product: Cc1noc(C)c1-c1c(-c2ccc(O)cc2)c2ccccc2n1S(=O)(=O)N(C)C
Temperature: 0 °C
Reaction time: 16 h
Yield: 27.2 %

Procedure:
2-(3,5-dimethylisoxazol-4-yl)-3-(4-methoxyphenyl)-N,N-dimethyl-1H-indole-1-sulfonamide (23 mg, 0.05 mmol) was dissolved in DCM and the mixture was cooled at 0° C. BF3.SMe2 (0.7 ml) was added drop wise and the reaction mixture was stirred in the fridge for 16 h. A few drops MeOH were added to the cool mixture. The mixture was then extracted with H2O/DCM using an isolute phase separator. Concentration gave a crude product which was purified using HPLC (40-70% AcN, 25 min gradient). 5.6 mg 2-(3,5-dimethylisoxazol-4-yl)-3-(4-hydroxyphenyl)-N,N-dimethyl-1H-indole-1-sulfonamide was obtained. ES/MS m/z: 412.06 (M+H), 410.16 (M−H); 1H NMR (acetone-d6, 500 MHz): 8.18 (m, 1H), 7.60 (m, 1H), 7.43 (m, 1H), 7.34 (m, 1H), 7.12 (m, 2H), 6.88 (m, 2H), 2.70 (s, 6H), 2.10 (s, 3H) and 2.09 (s, 3H).
Reaction SMILES: O[CH2:2][C@H:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.C(Br)(Br)(Br)[Br:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[Br:17][CH2:2][C@H:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1
Reactant: CC(C)(C)OC(=O)N1CCO[C@H](CO)C1
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCO[C@H](CBr)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 53.5 %

Procedure:
1,1-Dimethylethyl (2S)-2-(hydroxymethyl)-4-morpholinecarboxylate (18.5 g, 0.080 mol) and carbon tetrabromide (34.5 g, 0.104 mol) were dissolved in methylene chloride (400 mL) and cooled in an ice bath. A solution of triphenylphosphine (22 g, 0.084 mol) in methylene chloride (150 ml) was added dropwise over 30 min. After 1 hr at 0° C., the reaction was allowed warm to room temp and was stirred overnight. The reaction volume was reduced by ½ in vacuo and poured onto a pad of silica gel and the product eluted with 15% ethyl acetate in hexane. The filtrate was concentrated in vacuo to afford the desired compound as an oil (12 g, 55%). MS (ES)+ m/e 281 [M+H]+.
Reaction SMILES: [C:1]([O:20][CH2:21]C)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]>Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1>[C:1]([O:20][CH3:21])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OCC
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)(=Cc2ccccc2)[P](C2CCCCC2)(C2CCCCC2)C2CCCCC2)c(C)c1
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OC
Temperature: 60 °C
Reaction time: 8 h

Procedure:
A stainless steel autoclave with a glass liner was equipped with a magnetic stirrer bar and charged with ethyl oleate (0.34 g, 1.1 mmol) and Second Generation Grubbs Catalyst (9.3 mg, 0.11 μmol). The autoclave flushed with argon. The autoclave was evacuated and then pressurised with cis-2-butene to a pressure of 15 psi. The autoclave was heated at 60° C. with stirring overnight. The pressure was then released and ethyl vinyl ether (50 μL) added to the reaction mixture. A sample of the product was trans-esterified with methanol by conventional means and analysis of the trans-esterification product by GC showed a conversion of >85% of the oleic chains to 9-undecenoic chains.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C@H:14]2[NH:19][C@@H:18]([C:20](OC)=[O:21])[CH2:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1.O.[OH-].[Na+]>C1COCC1.C(OCC)(=O)C>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C@H:14]2[NH:19][C@@H:18]([CH2:20][OH:21])[CH2:17][CH2:16][CH2:15]2)=[CH:10][CH:9]=1
Reactant: COC(=O)[C@H]1CCC[C@@H](c2ccc(Cl)cc2)N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: OC[C@H]1CCC[C@@H](c2ccc(Cl)cc2)N1
Temperature: -20 °C
Reaction time: 1 h
Yield: 86.5 %

Procedure:
Lithium aluminum hydride (508 mg) was suspended in THF (50 mL) in a nitrogen atmosphere. Methyl (2R,6S)-6-(4-chlorophenyl)piperidine-2-carboxylate (2.47 g) was added to the suspension at −20° C., and the reaction solution was stirred at −20° C. for one hour. Water (0.51 ml), a 5 N sodium hydroxide solution (0.51 ml), and water (1.53 ml) were sequentially added to the reaction solution at −20° C., and the reaction solution was stirred at room temperature for 15 minutes. Ethyl acetate was added to the reaction solution. Then, the reaction solution was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system) to obtain 1.90 g of the title compound. The property value of the compound is as follows.
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH:14]2[C@@H:12](O2)[C:11](=[O:15])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:16][O:17][C:18](=[O:25])[CH2:19][S:20][CH2:21][CH2:22][CH2:23][SH:24].[Si](O[C@@H]1CC(=O)C=C1)(C(C)(C)C)(C)C>C(Cl)Cl>[CH3:16][O:17][C:18](=[O:25])[CH2:19][S:20][CH2:21][CH2:22][CH2:23][S:24][C:12]1[C:11](=[O:15])[CH2:10][C@@H:9]([O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3])[CH:14]=1
Reactant: COC(=O)CSCCCS
Reactant: CC(C)(C)[Si](C)(C)OC1CC(=O)[C@@H]2OC12
Agent: CC(C)(C)[Si](C)(C)O[C@H]1C=CC(=O)C1
Solvent: ClCCl
Product: COC(=O)CSCCCSC1=C[C@H](O[Si](C)(C)C(C)(C)C)CC1=O
Temperature: 0 °C
Reaction time: 18 h
Yield: 80 %

Procedure:
The epoxide 3 prepared above was diluted with CH2Cl2 (30 mL), (3-mercaptopropylsulfanyl) acetic acid methyl ester 4 (1.93 g, 10.7 mmol), prepared according to Chem. Pharm. Bull. 28 (2), 1980, 558-566, was added and the solution was cooled to 0° C. Basic alumina (11.9 g) was added and the reaction mixture was warmed to room temperature. After stirring for 18 h the mixture was filtered through celite and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, 6:1 hex/EtOAc) to yield 3.6 g (80%) of the above titled compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C@@H:5]([NH2:7])[CH3:6].[N+:11]([C:14]1[CH:19]=[C:18]([N+:20]([O-:22])=[O:21])[CH:17]=[CH:16][C:15]=1[S:23](Cl)(=[O:25])=[O:24])([O-:13])=[O:12].C(N(CC)C(C)C)(C)C>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:5]([NH:7][S:23]([C:15]2[CH:16]=[CH:17][C:18]([N+:20]([O-:22])=[O:21])=[CH:19][C:14]=2[N+:11]([O-:13])=[O:12])(=[O:24])=[O:25])[CH3:6])[CH:8]=[CH:9][CH:10]=1
Reactant: C[C@H](N)c1cccc(Br)c1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)Cl)c([N+](=O)[O-])c1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: C[C@H](NS(=O)(=O)c1ccc([N+](=O)[O-])cc1[N+](=O)[O-])c1cccc(Br)c1
Temperature: 25 °C
Reaction time: 19 h
Yield: 94.4 %

Procedure:
To a stirred ice-cooled solution of (S)-(−)-3-bromo-α-methylbenzylamine (832 mg, 4.16 mmol, from Chiragene) in 15.6 mL of THF was added 1.33 g (4.99 mmol, 1.20 eq.) of 2,4-dinitrobenzenesulfonyl chloride, followed by 1.08 mL (6.20 mmol, 1.49 eq.) of N,N-diisopropylethylamine. The ice bath was removed, and the mixture was stirred at room temperature for 19 h and then concentrated. The residue was taken up in EtOAc, washed with 2×H2O, dried over Na2SO4, filtered, and concentrated. The residue was sonicated in ca. 5 mL of EtOAc until a precipitate was formed. The mixture was diluted to ca. 25 mL with hexanes. Filtration afforded product as a tan solid (1.69 g, 94.4% yield).
Reaction SMILES: [H-].[Na+].[F:3][C:4]([F:8])([F:7])[CH2:5][OH:6].Cl[C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][N:17]=1)[C:13]#[N:14]>C1COCC1>[F:3][C:4]([F:8])([F:7])[CH2:5][O:6][C:10]1[CH:11]=[C:12]([CH:15]=[CH:16][N:17]=1)[C:13]#[N:14]
Reactant: N#Cc1ccnc(Cl)c1
Reactant: OCC(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: N#Cc1ccnc(OCC(F)(F)F)c1
Temperature: 25 °C

Procedure:
To the suspension of NaH (2.78 g, 0.11 mole) in THF 100 mL) 2,2,2-trifluoroethanol (10 g, 0.1 mol) was added slowly. The mixture was stirred at RT till it turned clear. A solution of 2-chloro-isonicotinonitrile (13.8 g, 0.1 mol) in THF (100 mL) was slowly added and stirred at reflux for 3 h. After filtration and concentration, the crude oily compound was purified through column chromatography providing pure compound as an oil.