Water → 1-[1-({4-[(3-Chlorophenoxy)methyl]phenyl}carbonyl)azetidin-3-yl]-4-(1,3-thiazol-2-ylcarbonyl)piperazine

HRID 1852623Notes

Reaction equation

HRID 1852623 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][CH2:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[CH:9][CH:8]=1.[NH:19]1[CH2:22][CH:21]([N:23]2[CH2:28][CH2:27][N:26]([C:29]([C:31]3[S:32][CH:33]=[CH:34][N:35]=3)=[O:30])[CH2:25][CH2:24]2)[CH2:20]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O>CCN(CC)CC.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][CH:18]=1)[O:5][CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:11]([N:19]2[CH2:20][CH:21]([N:23]3[CH2:24][CH2:25][N:26]([C:29]([C:31]4[S:32][CH:33]=[CH:34][N:35]=4)=[O:30])[CH2:27][CH2:28]3)[CH2:22]2)=[O:13])=[CH:14][CH:15]=1

Participants

7

Reactant 4

HCID 962WaterHCID 5846604-[(3-Chlorophenoxy)methyl]benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59625677(4-(Azetidin-3-yl)piperazin-1-yl)(thiazol-2-yl)methanone

Product 1

HCID 497838661-[1-({4-[(3-Chlorophenoxy)methyl]phenyl}carbonyl)azetidin-3-yl]-4-(1,3-thiazol-2-ylcarbonyl)piperazineYield 46.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of compound 35d (77 mg, 0.29 mmol), compound 5e (108 mg, 0.38 mmol) and HATU (165 mg, 0.44 mmol) in Et3N (1 mL) and DMF (3 mL) was stirred for 18 h, and then poured into water (10 mL). The mixture was then extracted with EtOAc (3×). The combined organic extracts were washed with brine (2×), dried over Na2SO4, filtered, and concentrated under reduced pressure. The resultant residue was purified by flash column chromatography, eluting with 5% MeOH/CH2Cl2, to give compound 453 (67 mg). MS m/z (M+H+) 497.1. 1H NMR (CD3OD): δ 7.95 (d, J=2.0 Hz, 1H), 7.8 (d, J=2.0 Hz, 1H), 7.65 (d, J=8.1 Hz, 2H), 7.51 (d, J=8.1 Hz, 2H), 7.25 (t, J=8.0 Hz, 1H), 7.02 (s, 1H), 6.90-6.98 (m, 2H), 5.15 (s, 2H), 4.32-4.45 (m, 2H), 4.15-4.25 (m, 2H), 4.00-4.10 (m, 1H), 3.70-3.82 (br. s, 2H), 2.47 (br. s., 4H).

Workup

  1. extractionThe mixture was then extracted with EtOAc (3×)
  2. washThe combined organic extracts were washed with brine (2×)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by flash column chromatography
  7. washeluting with 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-30cebcddf7b445c3adb4570eca4d3973
Source dataset
uspto-grants-2015_02
Patent number
US08962607B2

Reaction notes

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