Dimethylformamide → HCID 86656739, compound

HRID 1257733Notes

Reaction equation

HRID 1257733 reaction equation
[C:1]([O:4][C@H:5]([CH3:9])[C:6]([OH:8])=O)(=[O:3])[CH3:2].C(Cl)Cl.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1.CN(C)C=O.[C:49]1([S:55]([N:58]2[C:62]3=[N:63][CH:64]=[C:65]([NH2:73])[C:66]([NH:67][CH:68]4[CH2:72][CH2:71][O:70][CH2:69]4)=[C:61]3[CH:60]=[CH:59]2)(=[O:57])=[O:56])[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>>[C:49]1([S:55]([N:58]2[C:62]3=[N:63][CH:64]=[C:65]([NH:73][C:6]([C@H:5]([O:4][C:1](=[O:3])[CH3:2])[CH3:9])=[O:8])[C:66]([NH:67][CH:68]4[CH2:72][CH2:71][O:70][CH2:69]4)=[C:61]3[CH:60]=[CH:59]2)(=[O:56])=[O:57])[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=1

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 6344DichloromethaneHCID 8471TriethylamineHCID 5325906Propanoic acid, 2-(acetyloxy)-, (2R)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67347357HCID 67347357, compound

Product 1

HCID 86656739HCID 86656739, compoundYield 62.1%

Procedure

(R)-2-acetoxypropanoic acid (0.306 g, 2.32 mmol) was dissolved in methylene chloride (20 mL, 200 mmol;). Triethylamine (0.42 mL, 3.0 mmol;) was added, followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (0.972 g, 2.56 mmol;) dissolved in N,N-dimethylformamide (2 mL, 20 mmol;). After 15 minutes, 1-benzenesulfonyl-N-(tetrahydro-furan-3-yl)-1H-pyrrolo[2,3-b]pyridine-4,5-diamine (0.728 g, 2.03 mmol) was added and the reaction was stirred 64 h at room temperature. The volatiles were removed under reduced pressure and the residue was dissolved in 100 ml EtOAc. This was shaken with 50 ml saturated aqueous NaHCO3. The layers were separated and the aqueous phase was extracted with EtOAc (2×50 ml). The combined organics were dried with MgSO4, filtered and concentrated. This material was then dissolved in a minimum volume of CH2Cl2 and injected onto a 40 g silica gel column which had been equilibrated with heptane. It was then eluted with a gradient of 0% to 100% ethyl acetate in heptane. The product containing fractions were combined and evaporated under reduced pressure to give the title compound as a clear oil (0.596 g, 62%). 1H NMR (400 MHz, CDCl3) δ 8.15 (d, J=7.6 Hz, 2H), 7.88 (s, 1H), 7.60-7.43 (m, 4H), 7.21 (d, J=7.2 Hz, 1H), 6.62 (d, J=4.1 Hz, 1H), 5.11-4.95 (m, 2H), 4.59-4.48 (m, 1H), 4.01-3.74 (m, 4H), 2.33-2.21 (m, 1H), 2.19 (d, J=3.3 Hz, 3H), 2.03-1.95 (m, 1H), 1.59 (d, J=6.9 Hz, 3H).

Workup

  1. customThe volatiles were removed under reduced pressure
  2. dissolutionthe residue was dissolved in 100 ml EtOAc
  3. stirringThis was shaken with 50 ml saturated aqueous NaHCO3
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with EtOAc (2×50 ml)
  6. dry with materialThe combined organics were dried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThis material was then dissolved in a minimum volume of CH2Cl2
  10. washIt was then eluted with a gradient of 0% to 100% ethyl acetate in heptane
  11. additionThe product containing fractions
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-4a34b3dc2c1c4ba39f3e811da488d31a
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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