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

HRID 1023090Notes

Reaction equation

HRID 1023090 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-c0dd26c1a88b4aeb9cd3b54cf1730422
Source dataset
uspto-grants-2014_05
Patent number
US08722658B2

Reaction notes

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