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1-Hydroxybenzotriazole → (+/-)-2-(tert-butyldimethylsilyloxy)-N-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-3-phenylpropanamide

HRID 2075359
Notes
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Reaction equation

HRID 2075359 reaction equation
[Si:1]([O:8][CH:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:10]([OH:12])=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.C1C=CC2N(O)N=NC=2C=1.[CH:42]1[C:51]2[C:46](=[CH:47][C:48]([C:52]3[S:56][C:55]([NH2:57])=[N:54][N:53]=3)=[CH:49][CH:50]=2)[CH:45]=[CH:44][N:43]=1.C1C2C(=CC(C(O)=O)=CC=2)C=CN=1.ClC1C=NC=C2SC(C(O)=O)=CC=12>CN(C=O)C>[Si:1]([O:8][CH:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:10]([NH:57][C:55]1[S:56][C:52]([C:48]2[CH:47]=[C:46]3[C:51](=[CH:50][CH:49]=2)[CH:42]=[N:43][CH:44]=[CH:45]3)=[N:53][N:54]=1)=[O:12])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 185161084-Chlorothieno[2,3-c]pyridine-2-carboxylic acidHCID 19765118(+/-)-2-(Tert-butyldimethylsilyloxy)-3-phenylpropanoic acidHCID 22128831Isoquinoline-6-carboxylic acid
HCID 59694446
5-(Isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine

Product 1

HCID 67089607(+/-)-2-(tert-butyldimethylsilyloxy)-N-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-3-phenylpropanamideYield 26%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(±)-2-(tert-Butyldimethylsilyloxy)-3-phenylpropanoic acid (1.2 g, 4.3 mmol) was taken up in 18 mL of DMF. N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (1.4 g, 7.1 mmol) and HOBt (1.4 g, 11 mmol) were added. After 10 minutes, 5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-amine (0.81 g, 3.6 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) was added. The mixture was stirred overnight. It was then partitioned between 50 mL of EtOAc and 50 mL of aq. NH4Cl. The aqueous portion was extracted twice with 50 mL of EtOAc. The combined organic extracts were washed with water (3×50 mL) and brine (50 mL) and dried over MgSO4. The mixture was filtered and evaporated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluting with a gradient of 10% to 50% EtOAc in hexanes) to provide (±)-2-(tert-butyldimethylsilyloxy)-N-(5-(isoquinolin-6-yl)-1,3,4-thiadiazol-2-yl)-3-phenylpropanamide (0.45 g, 26%) as a yellow solid.

Workup

  1. additionwas added
  2. customIt was then partitioned between 50 mL of EtOAc and 50 mL of aq. NH4Cl
  3. extractionThe aqueous portion was extracted twice with 50 mL of EtOAc
  4. washThe combined organic extracts were washed with water (3×50 mL) and brine (50 mL)
  5. dry with materialdried over MgSO4
  6. filtrationThe mixture was filtered
  7. customevaporated under reduced pressure
  8. customThe residue was purified by flash chromatography on silica gel (
  9. washeluting with a gradient of 10% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a12f0fc83a5140bba1a99c39e1957210
Source dataset
uspto-grants-2011_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07919504B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes