Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCN=C=NCCCN(C)C.Cl.[O:13]=[C:14]1[N:18]([CH:19]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20]([OH:22])=O)[C:17]2[CH:29]=[CH:30][CH:31]=[CH:32][C:16]=2[NH:15]1.C1C=CC2N(O)N=NC=2C=1.[N:43]1[CH:48]=[CH:47][C:46]([N:49]2[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)=[CH:45][CH:44]=1.C(N(C(C)C)C(C)C)C.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[O:22]=[C:20]([N:52]1[CH2:53][CH2:54][N:49]([C:46]2[CH:47]=[CH:48][N:43]=[CH:44][CH:45]=2)[CH2:50][CH2:51]1)[CH:19]([N:18]1[C:17]2[CH:29]=[CH:30][CH:31]=[CH:32][C:16]=2[NH:15][C:14]1=[O:13])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: O=C(O)C(c1ccccc1)n1c(=O)[nH]c2ccccc21
Reactant: c1cc(N2CCNCC2)ccn1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(C(c1ccccc1)n1c(=O)[nH]c2ccccc21)N1CCN(c2ccncc2)CC1

Procedure:
179 mg (0.94 mmol) of EDCl were added to a solution of 193 mg (0.72 mmol) of (2-oxo-2,3-dihydrobenzimidazol-1-yl)phenylacetic acid (VIIId), 106 mg (0.79 mmol) of HOBt, 117 mg (0.72 mmol) of 1-pyridin-4-ylpiperazine and 0.49 ml (2.87 mmol) of ethyldiisopropylamine in dichloromethane (8 ml) while stirring in an ice-water bath. The reaction solution was slowly warmed and stirred at room temperature for 16 h. Half-saturated aqueous potassium carbonate solution was added, and the organic phase was separated off. The aqueous phase was extracted with ethyl acetate (4×50 ml) and the combined organic phases were washed with sat. NaHCO3 solution, dried over magnesium sulfate and concentrated under reduced pressure. The reaction product was used without further purification for the next reaction step. Yield:
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]2[CH2:14][N:15]([CH2:17][CH2:18][CH2:19]Cl)[CH2:16][CH:9]12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[Cl:27][C:28]1[CH:29]=[C:30]([NH:35][C:36]2[C:45]3[C:40](=[CH:41][C:42]([O:47][CH3:48])=[C:43]([OH:46])[CH:44]=3)[N:39]=[CH:38][N:37]=2)[CH:31]=[CH:32][C:33]=1[F:34]>CN(C=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]2[CH2:14][N:15]([CH2:17][CH2:18][CH2:19][O:46][C:43]3[CH:44]=[C:45]4[C:40](=[CH:41][C:42]=3[O:47][CH3:48])[N:39]=[CH:38][N:37]=[C:36]4[NH:35][C:30]3[CH:31]=[CH:32][C:33]([F:34])=[C:28]([Cl:27])[CH:29]=3)[CH2:16][CH:9]12)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: ClCCCN1CC2OCCN(Cc3ccccc3)C2C1
Reactant: COc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1cc2ncnc(Nc3ccc(F)c(Cl)c3)c2cc1OCCCN1CC2OCCN(Cc3ccccc3)C2C1
Temperature: 90 °C
Yield: 79.9 %

Procedure:
To a solution of 4-benzyl-6-(3-chloropropyl)octahydropyrrolo[3,4-b][1,4]oxazine (0.30 g) in DMF (5 mL) was added K2CO3 (0.59 g), 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.27 g) and tetrabutylammonium iodide (20 mg). The reaction mixture was heated at 90° C. for 18 h, cooled to room temperature. The mixture was diluted with CH2Cl2 (100 mL), washed with water (100 mL×3) and brine (100 mL), and dried over anhydrous Na2SO4. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to afford the title compound (390 mg, 79.59%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 579.1 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.07-2.09 (t, J=13.36 Hz, 2H), 2.09-2.10 (m, 1H), 2.40-2.43 (m, 1H), 2.66-2.68 (m, 2H), 2.70-2.78 (m, 2H), 3.00-3.02 (m, 1H), 3.08-3.13 (m, 1H), 3.65 (s, 3H), 3.77 (s, 1H), 3.99 (s, 3H), 4.02-4.04 (m, 1H), 4.20-4.22 (m, 2H), 5.30 (s, 1H), 7.13 (m, 1H), 7.26 (d, J=2.04 Hz, 1H), 7.30-7.31 (m, 1H), 7.56 (d, J=1.20 Hz, 5H), 7.81 (s, 1H), 7.90 (s, 1H), 7.92 (d, J=2.60 Hz, 1H), 8.64 (s, 1H) ppm.
Reaction SMILES: [C:1]([C:7]1[CH:18]=[CH:17][CH:16]=[CH:15][C:8]=1[C:9](N(C)OC)=[O:10])#[C:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH2:19]([Mg]Cl)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1>[C:1]([C:7]1[CH:18]=[CH:17][CH:16]=[CH:15][C:8]=1[C:9](=[O:10])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)#[C:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: Cl[Mg]Cc1ccccc1
Reactant: CCCCC#Cc1ccccc1C(=O)N(C)OC
Solvent: C1CCOC1
Product: CCCCC#Cc1ccccc1C(=O)Cc1ccccc1
Yield: 78 %

Procedure:
2-(1-Hexyn-1-yl)-N-methyl-N-(methyloxy)benzamide (158) (1.0 g, 4.08 mmol) was treated with benzylmagnesium chloride in THF at 0° C. to give 0.88 g (78%) of compound 171 as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 0.93 (t, J=7.2 Hz, 3H), 1.40-1.53 (m, 2H), 1.56-1.65 (m, 2H), 2.45 (t, J=7.1 Hz, 2H), 4.43 (s, 2H), 7.20-7.26 (m, 4H), 7.27-7.36 (m, 2H), 7.34-7.39 (m, 1H), 7.45-7.52 (m, 2H). LCMS (ESI): m/z 277 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:51])[CH2:5][CH2:6][CH2:7][NH:8][S:9]([C:12]1[CH:13]=[C:14]([CH:48]=[CH:49][CH:50]=1)[C:15]([NH:17][C:18]1[S:19][C:20]2[CH2:47][CH2:46][CH2:45][CH2:44][C:21]=2[C:22]=1[C:23]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34]2[CH:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][CH:35]=2)=[CH:28][CH:27]=1)=[O:24])=[O:16])(=[O:11])=[O:10])[CH3:2].[CH2:52](I)[CH3:53].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:51])[CH2:5][CH2:6][CH2:7][N:8]([CH2:52][CH3:53])[S:9]([C:12]1[CH:13]=[C:14]([CH:48]=[CH:49][CH:50]=1)[C:15]([NH:17][C:18]1[S:19][C:20]2[CH2:47][CH2:46][CH2:45][CH2:44][C:21]=2[C:22]=1[C:23]([NH:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][C:34]2[CH:43]=[CH:42][C:37]([C:38]([O:40][CH3:41])=[O:39])=[CH:36][CH:35]=2)=[CH:28][CH:27]=1)=[O:24])=[O:16])(=[O:11])=[O:10])[CH3:2]
Reactant: CCOC(=O)CCCNS(=O)(=O)c1cccc(C(=O)Nc2sc3c(c2C(=O)Nc2ccc(CCc4ccc(C(=O)OC)cc4)cc2)CCCC3)c1
Reactant: CCI
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)CCCN(CC)S(=O)(=O)c1cccc(C(=O)Nc2sc3c(c2C(=O)Nc2ccc(CCc4ccc(C(=O)OC)cc4)cc2)CCCC3)c1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
A mixture of 200 mg of methyl 4-{2-[4-({[2-({3-[(4-ethoxy-4-oxobutyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate, 0.059 mL of ethyl iodide, 113 mg of potassium carbonate, and 2.0 mL of DMF was stirred at 60° C. overnight. To the reaction mixture was added an aqueous citric acid solution, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine in this order, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-chloroform) to obtain 137 mg of methyl 4-{2-[4-({[2-({3-[(4-ethoxy-4-oxobutyl)(ethyl)sulfamoyl]benzoyl}amino)-4,5,6,7-tetrahydro-1-benzothiophen-3-yl]carbonyl}amino)phenyl]ethyl}benzoate as a yellow solid.
Reaction SMILES: [C:1]([O:5][C:6](=[O:33])[NH:7][CH2:8][CH2:9][CH2:10][NH:11][CH:12]([C:15]1[N:16]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:17](=[O:25])[C:18]2[C:23]([CH3:24])=[N:22][S:21][C:19]=2[N:20]=1)[CH2:13][CH3:14])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:41]1([CH3:50])[CH:46]=[CH:45][C:44]([C:47](Cl)=[O:48])=[CH:43][CH:42]=1>C(Cl)Cl>[C:1]([O:5][C:6](=[O:33])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([CH:12]([C:15]1[N:16]([CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:17](=[O:25])[C:18]2[C:23]([CH3:24])=[N:22][S:21][C:19]=2[N:20]=1)[CH2:13][CH3:14])[C:47](=[O:48])[C:44]1[CH:45]=[CH:46][C:41]([CH3:50])=[CH:42][CH:43]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CCC(NCCCNC(=O)OC(C)(C)C)c1nc2snc(C)c2c(=O)n1Cc1ccccc1
Reactant: Cc1ccc(C(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCC(c1nc2snc(C)c2c(=O)n1Cc1ccccc1)N(CCCNC(=O)OC(C)(C)C)C(=O)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of {3-[1-(5-benzyl-3-methyl-4-oxo-4,5-dihydro-isothiazolo[5,4-d]pyrimidin-6-yl)-propylamino]-propyl}-carbamic acid tert-butyl ester (method 10) (0.1 g, 0.21 mmol) and triethylamine (0.303 g, 3 mmol) in DCM (20 mL) at r.t. was added dropwise a solution of p-toluoyl chloride (0.1 g, 0.6 mmol) in DCM (10 mL). The resulting solution was stirred at r.t. for 30 min. after which the TLC showed the disappearance of the SM. The reaction mixture was diluted with DCM (60 mL) washed with satd. NaHCO3 (100 mL), water (100 mL), brine (100 mL) and dried (Na2SO4). Concentration of the organic layer provided the crude product which was purified by column (silica gel) chromatography using 20-30% EtOAc in hexanes as eluent. Yield was 0.117 g (94%). m/z 590 (MH+).
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[NH:4][N:3]=1.C(O)(=O)C.[S:23]1[C:27]([C:28]2[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=2)=[CH:26][N:25]=[CH:24]1>CO>[Cl:18][C:14]1[CH:13]=[C:12]([NH:11][C:9]2[N:8]=[CH:7][N:6]=[C:5]3[NH:4][N:3]=[C:2]([N:1]=[CH:32][C:31]4[CH:30]=[CH:29][C:28]([C:27]5[S:23][CH:24]=[N:25][CH:26]=5)=[CH:35][CH:34]=4)[C:10]=23)[CH:17]=[CH:16][CH:15]=1
Reactant: O=Cc1ccc(-c2cncs2)cc1
Reactant: Nc1n[nH]c2ncnc(Nc3cccc(Cl)c3)c12
Solvent: CO
Solvent: CC(=O)O
Product: Clc1cccc(Nc2ncnc3[nH]nc(N=Cc4ccc(-c5cncs5)cc4)c23)c1

Procedure:
Analogously to Example 32, 521 mg (2.00 mmol) of 3-amino-4-(3-chlorophenylamino)-1H-pyrazolo[3,4-d]pyrimidine (see Step 1.6) and 343 μl of acetic acid are dissolved in 50 ml of methanol and reacted with 567 mg (3.0 mmol) of 4-(thiazol-5-yl)-benzaldehyde to form 4-(3-chloro-phenylamino)-3-[{4-(thiazol-5yl)-phenyl}-methyleneamino]-1H-pyrazolo[3,4-d]pyrimidine. Reduction of the above intermediate in 30 ml of DMEU with 16 ml (16 mmol) of DIBAL-H, analogous working-up and digestion in diethyl ether yield 4-(3-chloro-phenylamino)-3-[4-(thiazol-5-yl)-benzylamino]-1H-pyrazolo[3,4-d]pyrimidine; m.p. 235° C.; TLC: Rf=0.42 (CHCl3/methanol/H2O/acetic acid=85:13:1.5:0.5); HPLC: tRet(grad20-100)=8.5; FABMS: (M+H)+=434.
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:27]([NH:29][CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[O:28])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:26])[NH:8][S:9]([C:12]1[C:24]([CH3:25])=[C:23]2[C:17]([O:18][C:19]([CH2:22]2)([CH3:21])[CH3:20])=[C:15]([CH3:16])[C:13]=1[CH3:14])(=[O:11])=[O:10].O>C1COCC1>[NH2:1][C@H:2]([C:27]([NH:29][CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])=[O:28])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:26])[NH:8][S:9]([C:12]1[C:24]([CH3:25])=[C:23]2[C:17]([O:18][C:19]([CH2:22]2)([CH3:20])[CH3:21])=[C:15]([CH3:16])[C:13]=1[CH3:14])(=[O:11])=[O:10]
Reactant: Cc1c(C)c(S(=O)(=O)NC(=N)NCCC[C@H](NC(=O)OCc2ccccc2)C(=O)NCC(=O)OC(C)(C)C)c(C)c2c1OC(C)(C)C2
Solvent: O
Solvent: C1CCOC1
Product: Cc1c(C)c(S(=O)(=O)NC(=N)NCCC[C@H](N)C(=O)NCC(=O)OC(C)(C)C)c(C)c2c1OC(C)(C)C2
Yield: 86 %

Procedure:
A solution of 30 g of Z-Arg(Pbf)-Gly-OtBu in 350 ml of THF is mixed with 3 g of water-moist Pd/C (10%) and the Z group is removed by hydrogenation under a gentle stream of H2. The catalyst is then filtered off and the solvent is removed. The residue is taken up in ethyl acetate and treated further as in Example 2.1. H-Arg(Pbf)-Gly-OtBu is obtained in a yield of 86%.
Reaction SMILES: C([O:3][C:4](=[O:20])[C@@H:5]([O:18][CH3:19])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:14][C:15]([OH:17])=O)=[CH:9][CH:8]=1)C.[CH3:21][N:22]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:23][CH2:24][CH2:25][NH2:26].C(O[C@@H](CC1C=CC(O[C@@H](C(=O)NCCC2C=CC(OC3C=CC=CC=3)=CC=2)C)=CC=1)C(O)=O)C>>[CH3:19][O:18][C@@H:5]([CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][C:15](=[O:17])[NH:26][CH2:25][CH2:24][CH2:23][N:22]([CH3:21])[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[CH:11][CH:12]=1)[C:4]([OH:3])=[O:20]
Reactant: CCOC(=O)[C@H](Cc1ccc(OCC(=O)O)cc1)OC
Reactant: CN(CCCN)c1ccccc1
Agent: CCO[C@@H](Cc1ccc(O[C@H](C)C(=O)NCCc2ccc(Oc3ccccc3)cc2)cc1)C(=O)O
Product: CO[C@@H](Cc1ccc(OCC(=O)NCCCN(C)c2ccccc2)cc1)C(=O)O

Procedure:
The title compound was prepared from (2S)-3-(4-carboxymethoxy-phenyl)-2-methoxy-propionic acid ethyl ester (PREPARATION 3, step 2) and N1-methyl-N1-phenyl-propane-1,3-diamine via the same procedure used for the preparation of (2S,1R)-2-ethoxy-3-(4-{1-[2-(4-phenoxy-phenyl)-ethylcarbamoyl]-ethoxy}-phenyl)propionic acid (Example 1, step 3) to produce a colorless oil. MS (ES) for C22H28N2O5 [M+H]+: 401.
Reaction SMILES: C(O)(=O)C.C[C@H](N)[C@H](O)C1C=CC=CC=1.Cl.[BH4-].[Na+].[Cl:19][C:20]1[CH:25]=[CH:24][C:23](/[CH:26]=[C:27](/[N:34]2[CH:38]=[N:37][CH:36]=[N:35]2)\[C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:22][CH:21]=1.Cl>ClC1C=CC=CC=1.CN(C)C=O.O>[Cl:19][C:20]1[CH:25]=[CH:24][C:23](/[CH:26]=[C:27](/[N:34]2[CH:38]=[N:37][CH:36]=[N:35]2)\[CH:28]([OH:33])[C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:22][CH:21]=1
Reactant: CC(C)(C)C(=O)/C(=C\c1ccc(Cl)cc1)n1cncn1
Agent: C[C@H](N)[C@H](O)c1ccccc1
Agent: Cl
Agent: [BH4-]
Solvent: CN(C)C=O
Solvent: CC(=O)O
Solvent: Clc1ccccc1
Product: CC(C)(C)C(O)/C(=C\c1ccc(Cl)cc1)n1cncn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96 %

Procedure:
In a nitrogen atmosphere, 0.393 g (0.0065 mole) of acetic acid was added to a suspension of 8.18 g (0.0436 mole) of (-)-norephedrine hydrochloride in 62.17 g of chlorobenzene, and then a solution of 1.815 g (0.0480 mole) of sodium borohydride in 9.35 g of dimethylformamide was added dropwise to this suspension at 5° to 10° C. for 1.5 hours. Thereafter, the resulting mixture was stirred at room temperature for 1 hour, and then a solution of 8.42 g (0.0291 mole; E/Z=99.8/0.2) of (E)-1-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-penten-3-one in 49.7 g of chlorobenzene was added at room temperature. The resulting mixture was stirred at the same temperature for 18 hours. The reaction solution was decomposed with addition of 17.50 g of 10% hydrochloric acid and 5 g of water, and the organic layer was separated, washed with water and concentrated under reduced pressure to obtain 8.15 g (+)-(E)-1-(4-chlorophenyl)-2-(1,2,4-triazol-1-yl)-4,4-dimethyl-1-penten-3-ol as a crystal. The conversion was 99.8%, and the composition of the product obtained was: E-form alcohol, 90.8%; saturated alcohol, 2.3%; and Z-form alcohol, 6.9%. The enantiomer ratio of the E-form alcohol was: (+)-isomer, 81.0% and (-)-isomer, 19.0%. The optical yield was 62.0%.
Reaction SMILES: [C:1]([C:4]1[CH:11]=[C:10]([Cl:12])[C:7]([C:8]#[N:9])=[C:6]([N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[C:5]=1[O:18][CH2:19][CH3:20])(=[O:3])[CH3:2].[BH4-].[Na+]>CO.C(OCC)(=O)C>[Cl:12][C:10]1[C:7]([C:8]#[N:9])=[C:6]([N:13]2[CH2:14][CH2:15][CH2:16][CH2:17]2)[C:5]([O:18][CH2:19][CH3:20])=[C:4]([CH:1]([OH:3])[CH3:2])[CH:11]=1
Reactant: CCOc1c(C(C)=O)cc(Cl)c(C#N)c1N1CCCC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CCOc1c(C(C)O)cc(Cl)c(C#N)c1N1CCCC1
Reaction time: 1 h
Yield: 101.8 %

Procedure:
The 4-acetyl-6-chloro-3-ethoxy-2-pyrrolidin-1-ylbenzonitrile (0.045 g, 0.15 mmol) was dissolved in methanol (3 mL) and cooled in an ice bath. The sodium tetrahydroborate (0.0058 g, 0.15 mmol) was added and the reaction was monitored by LC/MS. After stirring for 1 h, the reaction was taken up in ethyl acetate and washed with water, sodium bicarbonate, brine and dried over magnesium sulfate to give crude 6-chloro-3-ethoxy-4-(1-hydroxyethyl)-2-pyrrolidin-1-ylbenzonitrile as a clear oil (0.045 g, 100%). LCMS calculated for C15H20ClN2O2(M+H)+: m/z=295.1; found 295.1.
Reaction SMILES: C([O:4][C:5]1[CH:6]=[C:7]([CH:15]([CH3:21])[C:16]([O:18]CC)=O)[CH:8]=[CH:9][C:10]=1[O:11]C(=O)C)(=O)C.[CH2:22]([NH2:34])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]>>[CH2:22]([NH:34][C:16](=[O:18])[CH:15]([C:7]1[CH:8]=[CH:9][C:10]([OH:11])=[C:5]([OH:4])[CH:6]=1)[CH3:21])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: CCOC(=O)C(C)c1ccc(OC(C)=O)c(OC(C)=O)c1
Reactant: CCCCCCCCCCCCN
Product: CCCCCCCCCCCCNC(=O)C(C)c1ccc(O)c(O)c1

Procedure:
Ethyl 3,4-diacetoxyphenylpropionate and laurylamine were used to obtain N-Lauryl-3,4-dihydroxyphenylpropionamide by carrying out the same procedures as described in Example 1.
Reaction SMILES: [C:1]([C:4]1[S:8][C:7]2[CH2:9][CH2:10][CH2:11][CH:12]([NH:13]C(=O)C)[C:6]=2[CH:5]=1)(=[O:3])[CH3:2].[ClH:17]>O>[ClH:17].[C:1]([C:4]1[S:8][C:7]2[CH2:9][CH2:10][CH2:11][CH:12]([NH2:13])[C:6]=2[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)NC1CCCc2sc(C(C)=O)cc21
Agent: Cl
Solvent: O
Product: CC(=O)c1cc2c(s1)CCCC2N

Procedure:
The product from Example 23 (7.25 grams) is heated with 90 ml. of 1 N hydrochloric acid at reflux temperature for 8.5 hours and cooled. The mixture is diluted with water and extracted with methylene chloride. The aqueous layer is then evaporated to dryness using 2-propanol for facilitating removal of water. This gives 4.85 grams of 2-acetyl-4,5,6,7-tetrahydrobenzo[b]thiophen-4-amine hydrochloride.
Reaction SMILES: [CH3:1][O:2][CH2:3][C@@H:4]1[NH:9][CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1.[CH2:17]=O>[Pd].CO>[CH3:1][O:2][CH2:3][C@@H:4]1[N:9]([CH3:17])[CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1
Reactant: C=O
Reactant: COC[C@H]1CN(C(=O)OC(C)(C)C)CCN1
Agent: [Pd]
Solvent: CO
Product: COC[C@H]1CN(C(=O)OC(C)(C)C)CCN1C
Temperature: 25 °C
Reaction time: 4 h
Yield: 105.7 %

Procedure:
To a mixture of tert-butyl (3R)-3-(methoxymethyl)piperazine-1-carboxylate (206 mg), methanol (3.09 mL), and a 36% aqueous formaldehyde solution (187 mg) was added 10% palladium-supported carbon (50% wet product) (76 mg), followed by stirring at room temperature for 4 hours under a hydrogen gas atmosphere (1 atm). The reactant was filtered through celite and then the solvent was evaporated under reduced pressure to obtain tert-butyl (3R)-3-(methoxymethyl)-4-methylpiperazine-1-carboxylate (231 mg) as an oily material.
Reaction SMILES: Br[CH2:2][C:3]([CH:19]([F:21])[F:20])=[C:4]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1.[CH3:22][O:23][P:24]([O:27]C)[O:25][CH3:26]>>[F:11][C:8]1[CH:9]=[CH:10][C:5]([C:4]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[C:3]([CH:19]([F:21])[F:20])[CH2:2][P:24](=[O:27])([O:25][CH3:26])[O:23][CH3:22])=[CH:6][CH:7]=1
Reactant: Fc1ccc(C(=C(CBr)C(F)F)c2ccc(F)cc2)cc1
Reactant: COP(OC)OC
Product: COP(=O)(CC(=C(c1ccc(F)cc1)c1ccc(F)cc1)C(F)F)OC
Yield: 73.6 %

Procedure:
A solution of 2-bromomethyl-3,3-difluoro-1,1-bis(4-fluorophenyl)propene (0.5 g, 1.4 mmol) and trimethylphosphite (0.5 g, 4 mmol) was heated at relfux for 20 minutes. Excess trimethyl phosphite was removed in vacuo and the residue purified by chromatography on silica eluting with 40% ethyl acetate to give 0.4 g of the title compound as a viscous oil. MS(EI): m/e =388 for M+ of C18H17F4O3P.
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[CH:4]([CH:5]=[C:6]([CH3:8])[CH3:7])[CH:3]1[C:9](Cl)=[O:10].[F:13][C:14]([F:31])([F:30])[CH:15]([OH:29])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:17]=1.N1C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:7][C:6]([CH3:8])=[CH:5][CH:4]1[CH:3]([C:9]([O:29][CH:15]([C:14]([F:13])([F:30])[F:31])[C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:17]=2)=[O:10])[C:2]1([CH3:12])[CH3:1]
Reactant: OC(c1cccc(Oc2ccccc2)c1)C(F)(F)F
Reactant: CC(C)=CC1C(C(=O)Cl)C1(C)C
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CC(C)=CC1C(C(=O)OC(c2cccc(Oc3ccccc3)c2)C(F)(F)F)C1(C)C
Yield: 93.9 %

Procedure:
This compound was prepared in the manner of Example II using 3.3 g of 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarbonyl chloride, whose preparation is described in J. Sci. Food and Agriculture, 18, 325 (1967), 4.3 g of α-trifluoromethyl-3-phenoxybenzyl alcohol, and 1.5 g of pyridine in 50 ml of toluene. Volatiles were distilled from the crude reaction product at 90°/0.08 mm for 1/2 hour, then at 100°/0.08 mm for 3/4 hour through a short path Kugelrohr distillation system to give as a residue 6.3 g of α-trifluoromethyl-3-phenoxybenzyl 3-(2,2-dimethylvinyl)-2,2-dimethylcyclopropanecarboxylate. The ir spectrum was consistent with the assigned structure.
Reaction SMILES: [C:1]([NH:3][C:4](=[N:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[NH:16][CH:15]=[N:14][C:13]=1[CH3:17])SC)#[N:2].[CH2:18]([CH2:20][NH2:21])[OH:19]>C(O)C>[C:1]([NH:3][C:4]([NH:21][CH2:20][CH2:18][OH:19])=[N:7][CH2:8][CH2:9][S:10][CH2:11][C:12]1[NH:16][CH:15]=[N:14][C:13]=1[CH3:17])#[N:2]
Reactant: CSC(=NCCSCc1[nH]cnc1C)NC#N
Reactant: NCCO
Solvent: CCO
Product: Cc1nc[nH]c1CSCCN=C(NC#N)NCCO

Procedure:
A solution of N-cyano-N'-[2-((4-methyl-5-imidazolyl)methylthio)ethyl]-S-methylisothiourea (2.7 g) (British Specification No. 1397436) and ethanolamine (1.34 g) in ethanol (50 ml) was heated under reflux for 19 hours. Concentration followed by chromatographic purification on a column of silica gel with chlorofrom-methanol (10:1) as eluant and final recrystallisation from isopropyl alcohol -- acetonitrile gave the title compound, m.p. 146°-7°. (Found: C, 46.8; H, 6.5; N, 29.6; S, 11.2% C11H18N6OS requires: C, 46.8; H, 6.4; N, 29.8; S, 11.4%).
Reaction SMILES: C(C1OC1)Br.[NH:6]1[CH2:10][CH2:9][CH2:8][C:7]1=O.[K].[CH3:13][O:14][CH2:15][CH2:16][O:17]C>>[O:14]1[CH:13]2[CH:15]1[C:16](=[O:17])[N:6]([CH2:7][CH2:8][CH3:9])[CH2:10]2
Reactant: COCCOC
Reactant: O=C1CCCN1
Agent: BrCC1CO1
Agent: [K]
Product: CCCN1CC2OC2C1=O
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a 5 liter flask equipped with a stirrer, condenser, thermometer and dropping funnel was charged 604 g. (4.28 moles) epibromohydrin and 2150 ml. of ethyleneglycol dimethylether. To this solution was added, over a half hour period, 263.5 g. (2.14 moles) potassium pyrrolidone. The mixture was stirred 48 hours at 25° C. Potassium bromide was removed by filtration and the product distilled. The fraction boiling at 87° to 100° at 0.07 to 0.1 mm Hg was collected as 201.8 g. of product (67% of Theory) having a purity of 93% analyzed by gas chromatography. The reaction of this example can be described by the equation: ##STR36##
Reaction SMILES: [CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[C:3]([CH:14]=O)[N:2]=1.C(O)(=O)[CH2:17][C:18]([OH:20])=[O:19].N1CCCCC1>O>[CH:1]1[C:13]2[NH:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[C:3]([CH:14]=[CH:17][C:18]([OH:20])=[O:19])[N:2]=1
Reactant: O=Cc1cc2c(cn1)[nH]c1ccccc12
Reactant: O=C(O)CC(=O)O
Solvent: O
Solvent: C1CCNCC1
Product: O=C(O)C=Cc1cc2c(cn1)[nH]c1ccccc12
Yield: 94.7 %

Procedure:
A mixture of 2.0 g of beta-carboline-3-carboxaldehyde, 2.0 g of malonic acid, 40 ml of water-free pyridine and 0.1 ml of piperidine is heated in a steam bath for 4 h. The solvent is evacuated in vacuum and after adding 20 ml of 2-propanol, the precipitate is filtered off. 2.3 g of 3-(3-beta-carbolinyl)-acrylic acid with a m.p. of 240°-260° C. (decomposition) is obtained.
Reaction SMILES: [CH2:1]([O:5][C:6](=[O:23])[CH:7](OC(=O)C)[NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[CH2:2][CH2:3][CH3:4].[C:24]1([S:30][CH3:31])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(Cl)Cl>B(F)(F)F.CCOCC.CCCCCC>[CH2:1]([O:5][C:6](=[O:23])[CH:7]([C:27]1[CH:28]=[CH:29][C:24]([S:30][CH3:31])=[CH:25][CH:26]=1)[NH:8][C:9]([O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:10])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOC(=O)C(NC(=O)OCc1ccccc1)OC(C)=O
Reactant: CSc1ccccc1
Agent: FB(F)F
Solvent: ClCCl
Solvent: CCCCCC
Solvent: CCOCC
Product: CCCCOC(=O)C(NC(=O)OCc1ccccc1)c1ccc(SC)cc1

Procedure:
A solution of 1.6 g. (5.0 mmol.) of N-benzyloxycarbonyl-2-acetoxyglycine n-butyl ester, 1.0 g. (8.0 mmol.) of thioanisole and 10 drops of boron trifluoride etherate in 10 ml. of methylene chloride was stirred at 25° for 2 hours. The reaction mixture was diluted with hexane and chromatographed on silica gel with hexane followed by 1:1 chloroform-hexane to give the title compound.