Acetic Acid → HCID 24991163, compound

HRID 554872Notes

Reaction equation

HRID 554872 reaction equation
[NH:1]1[CH2:4][CH:3]([O:5][C:6]2[CH:11]=[CH:10][C:9]([N:12]3[CH2:17][CH2:16][C:15]4[N:18]=[C:19]([C:21]5[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=5)[S:20][C:14]=4[C:13]3=[O:28])=[CH:8][C:7]=2[O:29][CH3:30])[CH2:2]1.[C:31](O)(=O)C.C=O.C([BH3-])#N.[Na+]>O.CO>[Cl:27][C:24]1[CH:23]=[CH:22][C:21]([C:19]2[S:20][C:14]3[C:13](=[O:28])[N:12]([C:9]4[CH:10]=[CH:11][C:6]([O:5][CH:3]5[CH2:4][N:1]([CH3:31])[CH2:2]5)=[C:7]([O:29][CH3:30])[CH:8]=4)[CH2:17][CH2:16][C:15]=3[N:18]=2)=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 249911625-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one

Product 1

HCID 24991163HCID 24991163, compoundYield 50.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Mix 5-[4-(azetidin-3-yloxy)-3-methoxy-phenyl]-2-(4-chloro-phenyl)-6,7-dihydro-5H-thiazolo[5,4-c]pyridin-4-one (3.1 g, 7.01 mmol) with anhydrous MeOH (100 mL) and treat with acetic acid (4.0 mL, 69.8 mmol) and formaldehyde (1.6 mL, 21.30 mmol, as a solution in water). Stir the mixture at room temperature for 30 min and then treat with sodium cyanoborohydride (1.3 g, 19.6 mmol). Stir the mixture at room temperature overnight and concentrate in vacuo. Partition the resulting residue between CH2Cl2 (100 mL) and saturated NaHCO3 (100 mL). Remove the organic solution and extract the aqueous phase with additional CH2Cl2 (2×100 mL). Combine the organic solutions and wash with water (50 mL), then dry, filter, and concentrate in vacuo. Purify the crude material by flash chromatography, using 8% MeOH (2M NH3)/CH2Cl2 as eluent, to give 1.6 g (50%) of the title compound as a yellow solid. ES/MS m/z (35Cl) 456 [M+1]+.

Workup

  1. stirringStir the mixture at room temperature overnight
  2. concentrationconcentrate in vacuo
  3. customPartition the resulting residue between CH2Cl2 (100 mL) and saturated NaHCO3 (100 mL)
  4. customRemove the organic solution
  5. extractionextract the aqueous phase with additional CH2Cl2 (2×100 mL)
  6. washCombine the organic solutions and wash with water (50 mL)
  7. customdry
  8. filtrationfilter
  9. concentrationconcentrate in vacuo
  10. customPurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-9f381d9b895445748be40911f68b8842
Source dataset
uspto-grants-2011_11
Patent number
US08049013B2

Reaction notes

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