3-Aminopropionitrile → HCID 71262233, compound

HRID 540249Notes

Reaction equation

HRID 540249 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](OC(F)(F)F)[CH:10]=2)[N:5]=[C:4]([N:17]2[CH2:23][C:22]3[CH:24]=[CH:25][CH:26]=[CH:27][C:21]=3[S:20](=[O:29])(=[O:28])[CH2:19][CH2:18]2)[CH:3]=1.[NH2:30][CH2:31][CH2:32][C:33]#[N:34].[C:35]1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[O:28]=[S:20]1(=[O:29])[C:21]2[CH:27]=[CH:26][CH:25]=[CH:24][C:22]=2[CH2:23][N:17]([C:4]2[CH:3]=[C:2]([NH:34][CH2:33][CH2:32][C:31]#[N:30])[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:35])[CH:10]=3)[N:5]=2)[CH2:18][CH2:19]1

Participants

7

Reactant 4

HCID 16473-AminopropionitrileHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 712545694-(4-Chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide

Product 1

HCID 71262233HCID 71262233, compoundYield 697.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A flask containing 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (500 mg, 1.34 mmol, prepared in analogy to 4-(4-chloro-6-(trifluoromethoxy)quinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide in Example 17-1), 3-aminopropionitrile (140 mg, 2.01 mmol), tris(dibenzylideneacetone)dipalladium(0) (61.8 mg, 0.068 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (83.3 mg, 0.134 mmol), sodium tert-butoxide (257 mg, 2.68 mmol) and toluene (15 ml) was evacuated and then filled with nitrogen (balloon). After being stirred at 110° C. overnight, the resulting mixture was diluted with water (15 mL), and extracted with ethyl acetate (15 mL×4). The combined organic layers were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography (eluting with 10% methanol in dichloromethane) to afford 380 mg of the product as a white solid (yield was 70%). MS obsd. (ESI+) [(M+H)+] 407, 1H NMR (400 MHz, CD3OD) δ ppm 8.02-8.00 (m, 1 H), 7.90 (d, J=7.2 Hz, 1 H), 7.69-7.63 (m, 2 H), 7.51-7.45 (m, 2 H), 7.34-7.31 (m, 1 H), 6.10 (s, 1 H), 5.19 (s, 2 H), 4.55 (brs, 2 H), 3.73 (t, J=13.2 Hz, 2 H), 3.63 (t, J=10 Hz, 2 H), 2.85 (t, 2 H), 2.44 (s, 3 H).

Workup

  1. customwas evacuated
  2. additionfilled with nitrogen (balloon)
  3. additionthe resulting mixture was diluted with water (15 mL)
  4. extractionextracted with ethyl acetate (15 mL×4)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography (eluting with 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-91af57b99af8441e9a7d72da121c49c3
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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