Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14][CH2:15]CC(N)=O)=[C:10]([C:20]([F:23])([F:22])[F:21])[CH:9]=2)[CH:5]=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].[C:30]([C:32]1([NH:35][C:36]([C@H:38]2[N:42]([C:43]([C:45]3([CH3:48])[CH2:47][CH2:46]3)=[O:44])[CH2:41][C@@H](OS(C3C=CC=CC=3)(=O)=O)[CH2:39]2)=[O:37])[CH2:34][CH2:33]1)#[N:31]>O1CCCC1.CN(C)C(=O)C.O>[C:30]([C:32]1([NH:35][C:36]([C@@H:38]2[CH2:39][C@@H:15]([S:14][C:11]3[CH:12]=[CH:13][C:8]([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=4)=[CH:9][C:10]=3[C:20]([F:22])([F:21])[F:23])[CH2:41][N:42]2[C:43]([C:45]2([CH3:48])[CH2:46][CH2:47]2)=[O:44])=[O:37])[CH2:33][CH2:34]1)#[N:31]
Reactant: Cc1cc(-c2ccc(SCCC(N)=O)c(C(F)(F)F)c2)ccn1
Reactant: CC1(C(=O)N2C[C@@H](OS(=O)(=O)c3ccccc3)C[C@H]2C(=O)NC2(C#N)CC2)CC1
Agent: CC(C)(C)[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)N(C)C
Solvent: C1CCOC1
Product: Cc1cc(-c2ccc(S[C@@H]3C[C@@H](C(=O)NC4(C#N)CC4)N(C(=O)C4(C)CC4)C3)c(C(F)(F)F)c2)ccn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 110.6 %

Procedure:
3-[4-(2-Methyl-pyridin-4-yl)-2-trifluoromethyl-phenylsulfanyl]-propionamide (15.0 g, 44.1 mmol) was dissolved in tetrahydrofuran (75 mL), before sodium tert-butoxide (4.15 g, 43.2 mmol) was added and the fine suspension was stirred for 2 h at room temperature. N,N-dimethylacetamide (37 mL) was added and the solution was stirred for further 2 h. A solution of benzenesulfonic acid (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-methyl-cyclo-propanecarbonyl)-pyrrolidin-3-yl ester (15.7 g, 37.7 mmol) in N,N-dimethylacetamide (37 mL) was added and the brown, clear solution was stirred for 65 h at room temperature. After that, the mixture was diluted with cold water (240 mL) and extracted with tert-butyl methyl ether (1×180 mL, 5×90 mL). The combined organic extracts were washed with aqueous sodium carbonate solution (1 M, 90 mL) and brine (90 mL), dried over sodium sulfate and concentrated in vacuo to yield the title compound as a brown gum (22.05 g). The crude product (containing dimethylacetamide) was used in the next step without further purification. MS (EI): m/z=529.1 [M+H]+. 1H NMR (CDCl3, 400 MHz): δ 0.56-0.66 (m, 2H), 0.87-0.93 (m, 1H), 1.04-1.09 (m, 1H), 1.18-1.22 (m, 2H), 1.31 (s, 3H), 1.45-1.57 (m, 2H), 1.95-2.04 (m, 1H), 2.65 (s, 3H), 2.95-3.01 (m, 1H), 3.91 & 4.02 (ABX, JAB=11.3 Hz, JAX=5.6 Hz, JBX=6.5 Hz, each 1H), 4.14-4.22 (m, 1H), 4.66 (dd, J=4.3 Hz, 8.1 Hz, 1H), 7.31 (dd, J=1.5 Hz, 5.3 Hz, 1H), 7.37 (bs, 1H), 7.69 & 7.80 (ABX, JAB=8.2 Hz, JAX=0 Hz, JBX=2.0 Hz, each 1H), 7.93 (d, J=1.9 Hz, 1H), 8.06 (bs, 1H), 8.60 (d, J=5.1 Hz, 1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:32][CH2:33][CH2:34][OH:35])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:22]=[CH:21][C:20](B4OC(C)(C)C(C)(C)O4)=[CH:19][CH:18]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl[C:37]1[CH:42]=[CH:41][N:40]=[CH:39][N:38]=1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@:8]2([CH2:32][CH2:33][CH2:34][OH:35])[O:13][C:12](=[O:14])[N:11]([C@H:15]([C:17]3[CH:18]=[CH:19][C:20]([C:37]4[CH:42]=[CH:41][N:40]=[CH:39][N:38]=4)=[CH:21][CH:22]=3)[CH3:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: Clc1ccncn1
Reactant: C[C@@H](c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)OC1=O
Product: C[C@@H](c1ccc(-c2ccncn2)cc1)N1CC[C@](CCCO)(c2ccc(F)cc2)OC1=O

Procedure:
The title compound was prepared from (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-one and 4-chloropyrimidine following a procedure analogous to that described in Example 1 Step 2. LC-MS Method 2 tR=1.172, m/z=392.1; 1H NMR (CDCl3) 1.28-1.40 (m, 1H), 1.52 (m, 3H), 1.64 (m, 2H), 1.81-1.99 (m, 2H), 2.09-2.37 (m, 3H), 2.90 (m, 1H), 3.51 (t, 2H), 5.68 (m, 1H), 6.88-7.07 (m, 3H), 7.16-7.28 (m, 3H), 7.58 (m, 1H), 7.79 (d, 2H), 8.61-8.80 (d, 1H), 9.18 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[NH:8][CH2:7][C:6]=2[CH:16]=1.[CH3:17][C:18]1[CH:35]=[CH:34][CH:33]=[CH:32][C:19]=1[C:20]([NH:22][C:23]1[CH:31]=[CH:30][C:26]([C:27](Cl)=[O:28])=[CH:25][CH:24]=1)=[O:21].Cl>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]([C:27]([C:26]3[CH:25]=[CH:24][C:23]([NH:22][C:20](=[O:21])[C:19]4[CH:32]=[CH:33][CH:34]=[CH:35][C:18]=4[CH3:17])=[CH:31][CH:30]=3)=[O:28])[CH2:7][C:6]=2[CH:16]=1
Reactant: Clc1ccc2c(c1)CNc1ccccc1O2
Reactant: Cc1ccccc1C(=O)Nc1ccc(C(=O)Cl)cc1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2Cc3cc(Cl)ccc3Oc3ccccc32)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 51.2 %

Procedure:
To a mixture of 0.229 g (1.0 mmol) of 2-chloro-10,11-dihydrodibenz[b,f][1,4]oxazepine in 1.0 ml of pyridine under nitrogen is added 0.30 g (1.1 mmol) of 4-[(2-methylbenzoyl)amino]benzoyl chloride. The mixture is stirred at room temperature for 1 hour, heated on a steam bath for 5 minutes and 8 ml of 2N HCl added. The mixture is extracted with ethyl acetate and the extract washed three times with 1 ml of 1N sodium bicarbonate. The organic layer is dried (MgSO4) and the solvent removed. The residue is crystallized from ethyl acetate-hexane to give 0.24 g of crystals, m.p. 207°-208° C. Anal. Calc'd for C28H2N2 O3Cl: C,71.9; H,4.5; N,6.0; Cl,7.6. Found: C,71.6; H,4.6; N,5.9; Cl,7.4.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]([C:18]1[O:22][C:21]([C:23]2[CH:24]=[C:25]([CH:29]=[C:30]([N:32]([CH3:37])[S:33]([CH3:36])(=[O:35])=[O:34])[CH:31]=2)[C:26](O)=[O:27])=[N:20][N:19]=1)([CH3:17])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:38](N(C(C)C)CC)(C)C.C(Cl)CCl.C1C=N[C:54]2[N:57]([OH:60])N=NC=2C=1>C(Cl)(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([C:18]1[O:22][C:21]([C:23]2[CH:31]=[C:30]([N:32]([CH3:37])[S:33]([CH3:36])(=[O:35])=[O:34])[CH:29]=[C:25]([C:26]([N:57]([O:60][CH3:38])[CH3:54])=[O:27])[CH:24]=2)=[N:20][N:19]=1)([CH3:17])[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: CCN(C(C)C)C(C)C
Reactant: CN(c1cc(C(=O)O)cc(-c2nnc(C(C)(Cc3ccccc3)NC(=O)OC(C)(C)C)o2)c1)S(C)(=O)=O
Reactant: On1nnc2cccnc21
Solvent: ClC(Cl)Cl
Solvent: ClCCCl
Product: CON(C)C(=O)c1cc(-c2nnc(C(C)(Cc3ccccc3)NC(=O)OC(C)(C)C)o2)cc(N(C)S(C)(=O)=O)c1

Procedure:
To a slurry of 3-(5-{1-[(tert-butoxycarbonyl)amino]-1-methyl-2-phenylethyl}-1,3,4-oxadiazol-2-yl)-5-[methyl(methylsulfonyl)amino]benzoic acid (Intermediate VI) (0.303 g, 0.571 mmol) and Weinreb amine hydrochloride (0.111 g, 1.142 mmol) in 6 mL CHCl3 was added diisopropylethylamine (0.150 mL, 0.857 mmol), followed by EDC (0.154 g, 0.857 mmol) and HOAt (0.035 g, 0.228 mmol) After 7 days at rt, the reaction was quenched by the addition of brine. The layers were separated, the aqueous washed with CH2Cl2 (2×), the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated. Purification with normal phase chromatography (40->100% EA/hex) afforded tert-butyl[1-(5-{3-{[methoxy(methyl)amino]carbonyl}-5-[methyl(methylsulfonyl)amino]phenyl}-1,3,4-oxadiazol-2-yl)-1-methyl-2-phenylethyl]carbamate as a white foam. 1H NMR (CDCl3, 400 MHz) 8.21 (app t, J=1.5 Hz, 1H), 8.11 (app t, J=2.0 Hz, 1H), 7.90 (app t, J=1.5 Hz, 1H), 7.30-7.22 (m, 3H), 7.06-7.04 (m, 2H), 5.04 (br s, 1H), 3.60 (s, 3H), 3.42 (s, 3H), 3.39 (s, 3H), 2.90 (s, 3H), 1.69 (s, 3H), 1.41 (s, 9H). LCMS [M+H]+=574.
Reaction SMILES: [Br:1][C:2]1[C:3]2[CH2:31][NH:30][C:29](=[O:32])[C:4]=2[C:5]([C:23]2[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=2)=[N:6][C:7]=1[NH:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[NH:15]C(=O)OC(C)(C)C.[ClH:33].O1CCOCC1>>[ClH:33].[NH2:15][C@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]1[NH:8][C:7]1[N:6]=[C:5]([C:23]2[CH:24]=[N:25][N:26]([CH3:28])[CH:27]=2)[C:4]2[C:29](=[O:32])[NH:30][CH2:31][C:3]=2[C:2]=1[Br:1]
Reactant: Cn1cc(-c2nc(N[C@@H]3CCCC[C@@H]3NC(=O)OC(C)(C)C)c(Br)c3c2C(=O)NC3)cn1
Agent: Cl
Solvent: C1COCCO1
Product: Cn1cc(-c2nc(N[C@@H]3CCCC[C@@H]3N)c(Br)c3c2C(=O)NC3)cn1
Yield: 22.2 %

Procedure:
A solution of tert-butyl (1S,2R)-2-(7-bromo-4-(1-methyl-1H-pyrazol-4-yl)-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (10 mg, 0.020 mmol) in HCl-dioxane(999 μL, 4.00 mmol) was stirred at RT for 2 h. The mixture was concentrated to a residue, diluted with Et2O (3 mL), and sonicated to yield a white precipitate, which was filtered and dried overnight in a lyophilizer to give an HCl salt of the title compound as a white solid (1.8 mg, 21%). [M+H] calc'd for C17H21BrN6O, 406. found, 406.
Reaction SMILES: [CH2:1]([NH:3][C:4]1[C:13]2[C:8](=[C:9]([CH2:24][CH2:25][CH3:26])[C:10]3[O:17][C:16]([C:18]([O:20]CC)=[O:19])=[CH:15][C:14](=[O:23])[C:11]=3[CH:12]=2)[N:7]=[C:6]([C:27]([O:29]CC)=[O:28])[CH:5]=1)[CH3:2].[Na:32][Na].ClC1C2C=C(OC)C3C(=O)C=C(C([O-])=O)OC=3C=2N=C(C([O-])=O)C=1.[Na+].[Na+]>>[CH2:1]([NH:3][C:4]1[C:13]2[C:8](=[C:9]([CH2:24][CH2:25][CH3:26])[C:10]3[O:17][C:16]([C:18]([O-:20])=[O:19])=[CH:15][C:14](=[O:23])[C:11]=3[CH:12]=2)[N:7]=[C:6]([C:27]([O-:29])=[O:28])[CH:5]=1)[CH3:2].[Na+:32].[Na+:32]
Reactant: CCCc1c2nc(C(=O)OCC)cc(NCC)c2cc2c(=O)cc(C(=O)OCC)oc12
Reactant: [Na][Na]
Agent: COc1cc2c(Cl)cc(C(=O)[O-])nc2c2oc(C(=O)[O-])cc(=O)c12
Agent: [Na+]
Product: CCCc1c2nc(C(=O)[O-])cc(NCC)c2cc2c(=O)cc(C(=O)[O-])oc12

Procedure:
The product of step (c) was hydrolysed to the disodium salt by the method of Example 3 (g) to afford a cream solid.
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:8]2[S:21](=[O:23])(=[O:22])[CH2:20][CH2:19][CH2:18][C:9]=2[N:10]=[C:11]([CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[N:12]=1)(=O)=O.[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33][CH2:34][CH2:35][OH:36])=[CH:29][CH:28]=1>>[CH:13]1([C:11]2[N:12]=[C:7]([NH:26][C:27]3[CH:28]=[CH:29][C:30]([CH2:33][CH2:34][CH2:35][OH:36])=[CH:31][CH:32]=3)[C:8]3[S:21](=[O:23])(=[O:22])[CH2:20][CH2:19][CH2:18][C:9]=3[N:10]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: Nc1ccc(CCCO)cc1
Reactant: O=S1(=O)CCCc2nc(C3CCCC3)nc(OS(=O)(=O)C(F)(F)F)c21
Product: O=S1(=O)CCCc2nc(C3CCCC3)nc(Nc3ccc(CCCO)cc3)c21
Yield: 17.2 %

Procedure:
Following general procedure H, 2-cyclopentyl-5,5-dioxido-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidin-4-yl trifluoromethanesulfonate (0.215 g, crude) was reacted with 3-(4-aminophenyl)propan-1-ol (0.040 g, 0.26 mmol) to afford the title compound (0.018 g, 17%) as a white solid. MW=401.52. 1H NMR (DMSO-d6, 500 MHz) δ 8.56 (s, 1H), 7.51 (d, J=8.5 Hz, 2H), 7.19 (d, J=8.5 Hz, 2H), 4.44 (t, J=5.5 Hz, 1H), 3.70-3.65 (m, 2H), 3.45-3.38 (m, 2H), 3.09 (quin, J=8.0 Hz, 1H), 2.93 (t, J=6.5 Hz, 2H), 2.63-2.57 (m, 2H), 2.36-2.28 (m, 2H), 1.99-1.90 (m, 2H), 1.83-1.55 (m, 8H); APCI MS m/z 402 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[O:17][CH3:18])[CH2:5][O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][C:24](=[O:29])[C:23]2=[O:30]>>[Si:7]([O:6][CH2:5][C:4]1[CH:14]=[CH:15][C:16]([O:17][CH3:18])=[C:2]([C:23]2([OH:30])[C:22]3[C:26](=[CH:27][CH:28]=[C:20]([Cl:19])[CH:21]=3)[NH:25][C:24]2=[O:29])[CH:3]=1)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]
Reactant: COc1ccc(CO[Si](C)(C)C(C)(C)C)cc1Br
Reactant: O=C1Nc2ccc(Cl)cc2C1=O
Product: COc1ccc(CO[Si](C)(C)C(C)(C)C)cc1C1(O)C(=O)Nc2ccc(Cl)cc21
Yield: 60.5 %

Procedure:
With 100 g of the compound obtained in Step 204-2 and 45.8 g of 5-chloroisatin as starting material, 66.2 g of the title compound (opal solid) was obtained by a similar method to Step 21-1.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH:16]=[CH:17][NH:18]3)=[O:13])=[CH:8][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:29]([NH2:33])([CH3:32])([CH3:31])[CH3:30]>C(O)C>[CH3:30][C:29]([NH:33][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH:16]=[CH:17][NH:18]3)=[O:13])=[CH:8][CH:7]=1)([CH3:32])[CH3:31]
Reactant: O=C(c1ccc(OCCCCl)cc1)c1cccc2[nH]ccc12
Reactant: CC(C)(C)N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CC(C)(C)NCCCOc1ccc(C(=O)c2cccc3[nH]ccc23)cc1
Temperature: 140 °C

Procedure:
A mixture of 7.75 8 of the product of Step E, 6.83 g of potassium carbonate, 25.8 ml of tertbutylamine and 150 ml of ethanol was heated at 140° C. for 48 hours in an autoclave. After filtering, the filtrate was brought to dryness under reduced pressure and the 11.7 g of residue were chromatographed on silica (eluant: ethyl acetate-triethylamine (95-5)) to obtain 6.32 g of the desired product.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][CH3:14])=[C:5]([CH3:15])[C:4]=1[CH:16]=O.CO[C:20]1[C:29]2C(=CC=CC=2)C(OC)=C[C:21]=1/[CH:32]=[C:33](\C)/[C:34]([O:36][CH2:37][CH3:38])=[O:35]>>[CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][CH3:14])=[C:5]([CH3:15])[C:4]=1/[CH:16]=[C:33](\[CH2:32][CH2:21][CH2:20][CH3:29])/[C:34]([O:36][CH2:37][CH3:38])=[O:35]
Reactant: CCOC(=O)/C(C)=C/c1cc(OC)c2ccccc2c1OC
Reactant: COc1c(C)c(C=O)c(OC)c2ccccc12
Product: CCCC/C(=C\c1c(C)c(OC)c2ccccc2c1OC)C(=O)OCC

Procedure:
Compound 98b was prepared from 34 (0.383 g, 1.67 mmol) as described above for 28a to give 0.209 g (0.58 mmol, 34%) of the product as a colorless oil following flash chromatography (1:9 EtOAc:hexanes) and recrystallization from Et2O/hexanes.
Reaction SMILES: FC(F)(F)S([O:6][S:7]([C:10]([F:13])([F:12])[F:11])(=[O:9])=[O:8])(=O)=O.[C:16]([C:18]1[CH:19]=[C:20]([C:25]2[S:29][C:28]([C:30]([O:32][CH3:33])=[O:31])=[CH:27][CH:26]=2)[CH:21]=[CH:22][C:23]=1O)#[N:17]>N1C=CC=CC=1>[C:16]([C:18]1[CH:19]=[C:20]([C:25]2[S:29][C:28]([C:30]([O:32][CH3:33])=[O:31])=[CH:27][CH:26]=2)[CH:21]=[CH:22][C:23]=1[O:6][S:7]([C:10]([F:11])([F:12])[F:13])(=[O:8])=[O:9])#[N:17]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: COC(=O)c1ccc(-c2ccc(O)c(C#N)c2)s1
Solvent: c1ccncc1
Product: COC(=O)c1ccc(-c2ccc(OS(=O)(=O)C(F)(F)F)c(C#N)c2)s1
Temperature: 25 °C

Procedure:
Trifluoromethanesulfonic anhydride was added to a pyridine solution of methyl 5-(3-cyano-4-hydroxyphenyl)thiophene-2-carboxylate and the whole was stirred at room temperature to obtain methyl 5-(3-cyano-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)thiophene-2-carboxylate. F: 392.
Reaction SMILES: CSC.[CH3:4][O:5][C:6]1[CH:23]=[CH:22][C:9]([CH:10]=[N:11][S:12]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[CH:8][CH:7]=1.[C:24]1([CH:30]=[N+]=[N-])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>ClCCl.C(OC)(C)(C)C.C([O-])(=O)C.[Rh+2].C([O-])(=O)C>[CH3:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([C@H:10]2[C@H:30]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[N:11]2[S:12]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)(=[O:14])=[O:13])=[CH:22][CH:23]=1
Reactant: [N-]=[N+]=Cc1ccccc1
Reactant: COc1ccc(C=NS(=O)(=O)c2ccc(C)cc2)cc1
Agent: [Rh+2]
Agent: CC(=O)[O-]
Solvent: COC(C)(C)C
Solvent: CSC
Solvent: ClCCl
Product: COc1ccc([C@H]2[C@H](c3ccccc3)N2S(=O)(=O)c2ccc(C)cc2)cc1
Yield: 51 %

Procedure:
To a stirred solution of dimethylsulphide (7 μl, 0.1 mmol), rhodium (II) acetate (2 mg, 0.005 mmol) and N-(4-methoxybenzylidene)toluene-p-sulphonamide (144 mg, 0.5 mmol) in dichloromethane (2 ml) was added phenyldiazomethane (prepared as in Example 36; 8.96 ml of a 0.067M solution in t-butylmethylether) over a period of 12 hours. Upon completion of the addition the solvent was removed in vacuo and the residue was chromatographed using silica gel eluting with 15:85 ethyl acetate:petrol to give the title compound (96 mg, 51%). δH (CDCl3) 7.62(2H), 6.75-7.45(11H,m), 4.35(1H,d,J=6 Hz), 4.18(1H,d,J=6 Hz), 3.62(3H,s), 2.35(3H,s)ppm.
Reaction SMILES: [C:1]1([C@@:7]23[O:15][C:14]4[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=4[C@@H:8]2[CH2:9][NH:10][CH2:11][CH2:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:27][C:28]#[N:29]>CN(C)C=O.CCOCC>[C:28]([CH2:27][N:10]1[CH2:11][CH2:12][C@:7]2([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:15][C:14]3[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=3[C@@H:8]2[CH2:9]1)#[N:29]
Reactant: N#CCCl
Reactant: c1ccc([C@]23CCNC[C@H]2c2ccccc2O3)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: N#CCN1CC[C@]2(c3ccccc3)Oc3ccccc3[C@@H]2C1
Yield: 99.7 %

Procedure:
To a solution of 3.02 g of cis-1,2,3,4,4a,9b-hexahydro-4a-phenyl-benzofuro[3,2-c]pyridine in 48 ml of dry dimethylformamide was added 3.6 g of anhydrous potassium carbonate and 0.982 g of chloroacetonitrile. The resulting suspension was heated at 80° under nitrogen for 19 hours. The cooled reaction mixture was diluted with 500 ml of ether and washed with water (4×250 ml). The organic layer was dried over anhydrous Na2SO4 and evaporated in vacuo to give 3.48 g (99.9%) of a gum, which crystallized on standing. A 0.35 g portion of this material was recrystallized from ethanol to afford 0.22 g of crystals, m.p. s 93°, 94°-96°.
Reaction SMILES: C(OC([NH:11][C@@H:12]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:13][OH:14])=O)C1C=CC=CC=1.[NH2:22][C:23]1[C:24]([OH:34])=[C:25]([S:30]([OH:33])(=[O:32])=[O:31])[CH:26]=[C:27]([Cl:29])[CH:28]=1.Cl[C:36](Cl)([O:38]C(=O)OC(Cl)(Cl)Cl)Cl.N1C=CC=CC=1>C(Cl)Cl>[NH2:11][C@@H:12]([CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:13][O:14][C:36]([NH:22][C:23]1[C:24]([OH:34])=[C:25]([S:30]([OH:33])(=[O:32])=[O:31])[CH:26]=[C:27]([Cl:29])[CH:28]=1)=[O:38]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: O=C(N[C@H](CO)Cc1ccccc1)OCc1ccccc1
Reactant: Nc1cc(Cl)cc(S(=O)(=O)O)c1O
Solvent: c1ccncc1
Solvent: ClCCl
Product: N[C@H](COC(=O)Nc1cc(Cl)cc(S(=O)(=O)O)c1O)Cc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
285 mg (1 mmol) of (S)-2-(benzyloxycarbonylamino)-3-phenyl-1-propanol, 223 mg (1 mmol) of 3-amino-5-chloro-2-hydroxybenzenesulfonic acid and 100 mg (0.33 mmol) of triphosgene were suspended in 3 ml of methylene chloride, to which 0.7 ml of pyridine was dropwisely added. Following agitation at room temperature overnight, the solvent was distilled away, and the resultant was purified using purification step A to obtain a crude purified substance of the title compound in protected form. To the obtained crude purified substance, 2 ml of 48% hydrogen bromide-acetic acid solution was added, and the resultant was stirred at room temperature for 2 hours. The solvent was distilled away and water and acetonitrile were added to the obtained residue for deposition. The deposited solid substance was filtrated to obtain the title compound.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([OH:13])=O.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:21][CH2:22][O:23][CH:24]=[CH2:25].CO>O1CCOCC1.C(Cl)(Cl)Cl>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11]([CH2:25][CH2:24][O:23][CH:22]=[CH2:21])=[O:13]
Reactant: C=COCCCl
Reactant: O=C(O)c1ccc2ccccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: C=COCCC(=O)c1ccc2ccccc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.5 %

Procedure:
In a 300 mL three necked oven dried round bottom flask equipped with a magnetic stirrer, 25 g (0.145 mol) of 2-naphthoic acid and 24.07 g (0.17 mol) of potassium carbonate (K2CO3) were suspended in 100 ml of dioxane and the mixture stirred at room temperature for 1 hour, forming a thick slurry. 18.53 g (0.17 mol) of 2-chloroethylvinyl ether dissolved in 10 ml of dioxane was slowly added to the reaction mixture using a dropping funnel over a period of 1 hour and the reaction refluxed overnight for another 12 hours until a complete reaction was ascertained by thin layer chromatography (TLC) analysis (silica plates; eluant 1% (v/v) methanol in chloroform). The reaction was quenched by pouring the mixture slowly into 400 ml of 0.01% (v/v) hydrochloric acid (HCl) solution, the crude product was extracted into 300 ml of ethyl acetate, and the ethyl acetate extract was washed sequentially with water and brine to neutral pH. The ethyl acetate extracts were then dried over sodium sulfate, filtered and concentrated by rotary evaporation to afford 32 g (92% yield) of an amber oil which solidifies upon standing. The product was used without further purification. 1H NMR (500 MHz, Acetone-d6): δ 8.64 (s, 1H), 8.08 (d, 2H, 8 Hz), 7.89 (d, 2H, 8.5 Hz), 7.64-7.59 (q, 2H), 6.56-6.52 (d/d, 1H, 7 Hz), 5.58 (s, 1H), 4.60 (m, 2H), 4.49 (m, 2H), 2.30 (s, 3H), 1.90 (s, 3H). 13C NMR (125 MHz, CDCl3): δ 166.6, 151.5, 135.6, 132.4, 131.3, 129.4, 128.3, 128.1, 127.7, 127.0, 126.6, 125.2, 87.1, 65.9, 63.3.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([C:14](O)=[O:15])[CH:5]=[CH:4][C:3]1=2.S(Cl)(Cl)=O.[NH2:22][C:23]1[CH:37]=[CH:36][C:26]([O:27][CH2:28][CH2:29][N:30]2[CH2:35][CH2:34][O:33][CH2:32][CH2:31]2)=[CH:25][CH:24]=1>O1CCCC1.N1C=CC=CC=1>[CH3:1][C:2]1([CH3:17])[CH2:11][CH2:10][C:9]([CH3:12])([CH3:13])[C:8]2[CH:7]=[C:6]([C:14]([NH:22][C:23]3[CH:24]=[CH:25][C:26]([O:27][CH2:28][CH2:29][N:30]4[CH2:35][CH2:34][O:33][CH2:32][CH2:31]4)=[CH:36][CH:37]=3)=[O:15])[CH:5]=[CH:4][C:3]1=2
Reactant: CC1(C)CCC(C)(C)c2cc(C(=O)O)ccc21
Reactant: Nc1ccc(OCCN2CCOCC2)cc1
Solvent: O=S(Cl)Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CC1(C)CCC(C)(C)c2cc(C(=O)Nc3ccc(OCCN4CCOCC4)cc3)ccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 54.3 %

Procedure:
In a manner analogous to Example 1, 52.5 g of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxylic acid were converted by reaction with 200 ml of thionyl chloride into the acid chloride and, after dissolution in 200 ml of tetrahydrofuran added dropwise to a solution of 48.8 g of 4-[2-(4-amino-phenoxy)ethyl)-morpholine in 400 ml of pyridine while cooling slightly. The temperature should not rise above 30° C. After stirring at room temperature for 1 hour the reaction mixture was poured on to ice-water, extracted with ethyl acetate, the organic phase was washed with ice-cold 2N hydrochloric acid, dried and evaporated. The crystalline crude product was purified by filtration over a silica gel column (eluting agent hexane/ethyl acetate 1:4, then ethyl acetate, then ethyl acetate/ethanol=1:1) and recrystallized from hexane/ ethyl acetate. There were obtained 52 g of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-4'-(2-morpholinoethoxy)-2-naphthalenecarboxanilide in white crystals, m.p. 134°-136° C.