1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 57991863, compound

HRID 2075362Notes

Reaction equation

HRID 2075362 reaction equation
C(OC([C@@H:8]([C@@H:12]([C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=1)[CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[C:9]([OH:11])=O)=O)(C)(C)C.CC[N:34]=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH:53]1[C:62]2[C:57](=[CH:58][C:59]([C:63]3[S:67][C:66]([NH2:68])=[N:65][N:64]=3)=[CH:60][CH:61]=2)[CH:56]=[CH:55][N:54]=1.[CH:69]1[C:78]2[C:73](=CC(C(O)=O)=C[CH:77]=2)C=CN=1.ClC1C=NC=C2SC([C:92]([OH:94])=[O:93])=CC=12>CN(C=O)C>[CH:53]1[C:62]2[C:57](=[CH:58][C:59]([C:63]3[S:67][C:66]([NH2:68])=[N:65][N:64]=3)=[CH:60][CH:61]=2)[CH:56]=[CH:55][N:54]=1.[Si:15]([O:14][CH2:13][C@@H:12]([C:22]1[CH:23]=[CH:24][C:25]([C:28]([F:30])([F:31])[F:29])=[CH:26][CH:27]=1)[C@H:8]([NH:34][C:92](=[O:93])[O:94][C:78]([CH3:77])([CH3:69])[CH3:73])[C:9]([NH:68][C:66]1[S:67][C:63]([C:59]2[CH:58]=[C:57]3[C:62](=[CH:61][CH:60]=2)[CH:53]=[N:54][CH:55]=[CH:56]3)=[N:64][N:65]=1)=[O:11])([C:18]([CH3:21])([CH3:19])[CH3:20])([CH3:16])[CH3:17]

Participants

9

Reactant 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 185161084-Chlorothieno[2,3-c]pyridine-2-carboxylic acidHCID 22128831Isoquinoline-6-carboxylic acidHCID 596944465-(Isoquinolin-6-yl)-1,3,4-thiadiazol-2-amineHCID 67089215HCID 67089215, compound

Product 2

HCID 57991863HCID 57991863, compoundYield 54%HCID 596944465-(Isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To (2S,3S)-2-(tert-butoxycarbonyl)-4-(tert-butyldimethylsilyloxy)-3-(4-(trifluoromethyl)phenyl)butanoic acid (0.11 g, 0.23 mmol) in 3 mL of DMF was added EDCI (0.065 g, 0.34 mmol) and HOBt (0.062 g, 0.46 mmol). After 10 minutes, 5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine (0.057 g, 0.25 mmol) was added. 5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine was 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. The mixture was stirred for 12 hours. The solvent was removed under reduced pressure and the residue was taken up in 20 mL of EtOAc. The mixture was washed with aq NH4Cl (5 mL), water (5×5 mL), and brine (5 mL), then dried over MgSO4. The mixture was filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluting with a gradient from 0 to 2.5% MeOH in DCM) to provide tert-butyl (2S,3S)-4-(tert-butyldimethylsilyloxy)-1-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-ylamino)-1-oxo-3-(4-trifluoromethylphenyl)butan-2-ylcarbamate (0.086 g, 54%) as a yellow solid. 1H NMR (400 MHz, CD3OD): δ ppm 9.38 (s, 1H), 8.61-8.58 (m, 2H), 8.40 (d, J=8.9, 1H), 8.32 (d, 8.6 Hz, 1H), 8.06 (s, 1H), 8.04 (d, J=5.8 Hz, 1H), 7.70 (d, J=7.9 Hz, 2H), 7.61 (d, J=8.1 Hz, 2H), 5.01-4.95 (m, 1H), 4.11-3.96 (m, 2H), 3.62-3.55 (m, 1H), 1.38 (s, 9H), 0.87 (s, 9H), 0.02 (s, 3H), 0.00 (s, 3H). 1H not detected.

Workup

  1. customThe solvent was removed under reduced pressure
  2. washThe mixture was washed with aq NH4Cl (5 mL), water (5×5 mL), and brine (5 mL)
  3. dry with materialdried over MgSO4
  4. filtrationThe mixture was filtered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel (
  7. washeluting with a gradient from 0 to 2.5% MeOH in DCM)

Sources & evidence

ORD record
ord-28a234ec55764686a4f89044d123c294
Source dataset
uspto-grants-2011_04
Patent number
US07919504B2

Reaction notes

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