Sodium hydride → US10112934, Example 7
Reaction equation
[CH3:1][C:2]([N:7]([CH3:15])[CH2:8][CH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)([CH3:6])[C:3]([OH:5])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[H-].[Na+].[NH2:51][C:52]1[S:56][C:55]([C:57]([CH3:61])([CH3:60])[C:58]#[N:59])=[N:54][N:53]=1>CN(C=O)C>[C:58]([C:57]([CH3:61])([CH3:60])[C:55]1[S:56][C:52]([NH:51][C:3](=[O:5])[C:2]([CH3:1])([N:7]([CH3:15])[CH2:8][CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH3:6])=[N:53][N:54]=1)#[N:59]Participants
7
Reactant 5
HCID 24758Sodium hydride
HCID 81531Diisopropylethylamine
HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)
HCID 582972562-Methyl-2-[methyl-(tetrahydro-pyran-4-ylmethyl)-amino]-propionic acid2×
HCID 1176509032-(5-Amino-1,3,4-thiadiazol-2-yl)-2-methylpropanenitrile2×Product 1
Reagents, catalysts & solvents 1
Procedure
To 270 mg (1.25 mmol) of 2-methyl-2-[methyl-(tetrahydro-pyran-4-ylmethyl)-amino]-propionic acid (intermediate 3) in DMF (3 mL) are added 450 μL (2.58 mmol) DIPEA and 480 mg (1.26 mmol) HATU. In a second flask 110 mg sodium hydride (60% dispersion in oil; 2.75 mmol) are added to 215 mg (1.27 mmol) 2-(5-amino[1,3,4]thiadiazol-2-yl)-2-methyl-propionitrile (intermediate 6) in DMF (3 mL). After 10 min this mixture is added to the activated acid. The reaction mixture is stirred for additional 30 min, then filtered and purified by HPLC-MS to afford 50 mg of N-[5-(cyano-dimethyl-methyl)-[1,3,4]thiadiazol-2-yl]-2-methyl-2-[methyl-(tetrahydro-pyran-4-ylmethyl)-amino]-propionamide.
Workup
- additionAfter 10 min this mixture is added to the activated acid
- filtrationfiltered
- custompurified by HPLC-MS
Sources & evidence
- ORD record
- ord-8376e032ea864e9d8eb6688f29bc4b67
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08865744B1
Reaction notes
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