1,2-Dichloroethane → HCID 57991961, compound

HRID 2075345Notes

Reaction equation

HRID 2075345 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[S:15][C:14]([NH2:16])=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C1C2C(=CC(C(O)=O)=CC=2)C=CN=1.ClC1C=NC=C2SC(C(O)=O)=CC=12.[C:43]([O:47][C:48]([N:50]1[CH2:54][CH2:53][C@H:52]([C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[C@@H:51]1[C:61](O)=[O:62])=[O:49])([CH3:46])([CH3:45])[CH3:44].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH4+].[Cl-]>CN(C=O)C.C(Cl)Cl.O>[CH:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]3[S:15][C:14]([NH:16][C:61]([C@H:51]4[C@@H:52]([C:55]5[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=5)[CH2:53][CH2:54][N:50]4[C:48]([O:47][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:49])=[O:62])=[N:13][N:12]=3)=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

12

Reactant 8

HCID 111,2-DichloroethaneHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 185161084-Chlorothieno[2,3-c]pyridine-2-carboxylic acidHCID 22128831Isoquinoline-6-carboxylic acidHCID 57032840HCID 57032840, compoundHCID 596944465-(Isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine

Product 1

HCID 57991961HCID 57991961, compoundYield 30.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine (97 mg, 0.42 mmol) (prepared as shown in Scheme 5 using isoquinoline-6-carboxylic acid, commercially available from AstaTech Product List (Order Number 62874), instead of 4-chlorothieno[2,3-c]pyridine-2-carboxylic acid) and (±)-cis-1-(tert-butoxycarbonyl)-3-phenylpyrrolidine-2-carboxylic acid ((Damour et al. Synlett 1999, 2, 189-192), 149 mg, 0.51 mmol) in DMF (5.0 mL) was added EDC (122 mg, 0.64 mmol), HOBt (86 mg, 0.64 mmol) and DIEA (0.22 mL, 1.3 mmol). The mixture was stirred at room temperature for 24 hours. Aqueous NH4Cl (5 mL), water (5 mL) and DCM (10 mL) were added. The aqueous layer was extracted with DCM (3×10 mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The crude residue was purified by flash column chromatography (eluting with a gradient from DCM to 5% MeOH in DCM) to provide (±)-cis-tert-butyl 2-((5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)carbamoyl)-3-phenylpyrrolidine-1-carboxylate as a white foam (64 mg, 30%). LCMS (M+H) 502.2 calc. for C27H28N5O3S 502.2.

Workup

  1. customprepared
  2. extractionThe aqueous layer was extracted with DCM (3×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash column chromatography (
  7. washeluting with a gradient from DCM to 5% MeOH in DCM)

Sources & evidence

ORD record
ord-b9a2bb96e3714317bc2e0c9584bf3765
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

Loading…