HCID 2060469, compound → HCID 71656571, compound

HRID 928226Notes

Reaction equation

HRID 928226 reaction equation
C(SC1N=C(C)C=CC=1C(O)=O)C=C.[CH2:15]([O:18][C:19]1[CH:24]=[CH:23][C:22]([CH2:25][C@H:26]([NH:35][C:36](=[O:48])[C:37]2[CH:42]=[CH:41][C:40]([CH3:43])=[N:39][C:38]=2[S:44][CH2:45][CH:46]=[CH2:47])[C:27]([NH:29][C:30]2([C:33]#[N:34])[CH2:32][CH2:31]2)=[O:28])=[CH:21][C:20]=1[Cl:49])C=C>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1>[C:33]([C:30]1([NH:29][C:27]([C@H:26]2[NH:35][C:36](=[O:48])[C:37]3[C:38](=[N:39][C:40]([CH3:43])=[CH:41][CH:42]=3)[S:44][CH2:45][CH:46]=[CH:47][CH2:15][O:18][C:19]3=[CH:24][CH:23]=[C:22]([CH:21]=[C:20]3[Cl:49])[CH2:25]2)=[O:28])[CH2:31][CH2:32]1)#[N:34]

Participants

5

Reactant 2

HCID 2060469HCID 2060469, compoundHCID 89689474HCID 89689474, compound

Product 1

HCID 71656571HCID 71656571, compound

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 178425456HCID 178425456, compoundCatalyst

Conditions

Temperature
50 °C

Procedure

The title compound was prepared in analogy to example 8 starting from 2-(allylthio)-6-methylnicotinic acid with the exception of the macroccyclisation: in a 10 mL round-bottomed flask, (S)—N-(3-(4-(allyloxy)-3-chlorophenyl)-1-(1-cyanocyclopropylamino)-1-oxopropan-2-yl)-2-(allylthio)-6-methylnicotinamide (50 mg, 97.8 μmol, Eq: 1.00) was combined with dry degassed DCM (50 mL) under argon atmosphere and titanium (IV) isopropoxide (16.7 mg, 17.2 μL, 58.7 μmol, Eq: 0.60) was added. This solution was added dropwise (20 min) to a solution of Grubbs II (24.9 mg, 29.4 μmol, Eq: 0.30) dissolved in dry degassed DCM (35 ml) under argon atmosphere at 50° C. (reflux). After the addition, the reaction mixture was heated to 50° C. and stirred for 3 days under argon atmosphere. The crude material was purified by flash chromatography (silica gel, 20 g, n-heptane/AcOEt 2/1, 1/1) to yield a brown solid (4 mg; 6%). m/z=483.0 [M+H]+.

Workup

  1. customwith dry
  2. customdegassed DCM (50 mL) under argon atmosphere
  3. dissolutiondissolved
  4. customin dry
  5. customdegassed DCM (35 ml) under argon atmosphere at 50° C.
  6. temperature(reflux)
  7. additionAfter the addition
  8. customThe crude material was purified by flash chromatography (silica gel, 20 g, n-heptane/AcOEt 2/1, 1/1)
  9. customto yield a brown solid (4 mg; 6%)

Sources & evidence

ORD record
ord-b89e352240764ac09eed7d6cb8e151b9
Source dataset
uspto-grants-2016_03
Patent number
US09290467B2

Reaction notes

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