Diisopropylethylamine → 2-[4-[[2-(3-Chlorophenyl)-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidin-4-yl]amino]phenyl]-N-cyano-acetamide

HRID 1509064Notes

Reaction equation

HRID 1509064 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH2:25][C:26](O)=[O:27])=[CH:21][CH:20]=3)[C:11]3[S:17][CH2:16][CH2:15][CH2:14][C:12]=3[N:13]=2)[CH:5]=[CH:6][CH:7]=1.C[N:30]([C:32](ON1N=NC2C=CC=NC1=2)=[N+:33](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([CH2:25][C:26]([NH:33][C:32]#[N:30])=[O:27])=[CH:23][CH:24]=3)[C:11]3[S:17][CH2:16][CH2:15][CH2:14][C:12]=3[N:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 901101602-[4-[[2-(3-Chlorophenyl)-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidin-4-yl]amino]phenyl]acetic acid

Product 1

HCID 901117042-[4-[[2-(3-Chlorophenyl)-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidin-4-yl]amino]phenyl]-N-cyano-acetamideYield 20%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 8-mL vial was charged with 2-[4-[[2-(3-Chlorophenyl)-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidin-4-yl]amino]phenyl]acetic acid (95 mg, 0.23 mmol, 1 eq.), cyamide (15 mg, 0.36 mmol, 1.5 eq.), HATU (130 mg, 0.36 mmol, 1.5 eq.), diisopropylethylamine (90 mg, 0.69 mmol, 3 eq.) and DMF (1 ml). The resulting mixture was stirred at rt overnight until the starting acid was consumed. The mixture was added to NaHCO3 aq. (5 ml) and extracted with ethyl acetate (3×5 ml). The organic layers were combined and dried over Na2SO4. Removal of solvent gave a residue, which was purified by chromatography on silica gel using a preparation TLC plate and 2% of MeOH in DCM as mobile phase to give the title compound as a white solid (20 mg, 20% yield). MW=435.93. 1H NMR (400 MHz, methanol-d4) δ 8.19 (s, 1H), 8.11 (d, J=7.2 Hz, 1H), 7.65 (d, J=8.4 Hz, 2H), 7.43 (m, 2H), 7.32 (d, J=8.4 Hz, 2H), 3.69 (s, 2H), 3.18 (t, J=5.6 Hz, 2H), 2.94 (d, J=6.4 Hz, 2H), 2.27 (m, 2H).

Workup

  1. customwas consumed
  2. additionThe mixture was added to NaHCO3 aq. (5 ml)
  3. extractionextracted with ethyl acetate (3×5 ml)
  4. dry with materialdried over Na2SO4
  5. customRemoval of solvent
  6. customgave a residue, which
  7. customwas purified by chromatography on silica gel using
  8. customa preparation TLC plate and 2% of MeOH in DCM as mobile phase

Sources & evidence

ORD record
ord-b08bec5e2dce4f57bbc4805305554ee1
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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