Water → HCID 59351196, compound

HRID 555852Notes

Reaction equation

HRID 555852 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1.Cl[C:19]1[C:20]([C:25]2(C(OC)=O)[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[N:21][CH:22]=[CH:23][N:24]=1.[C:35](=O)([O-])[O-].[Cs+].[Cs+].O>CS(C)=O.[Cl-].[Na+].O>[CH3:35][N:10]([C:11]1[CH:16]=[CH:15][C:14]([O:17][C:19]2[C:20]([CH:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[N:21][CH:22]=[CH:23][N:24]=2)=[CH:13][CH:12]=1)[C:2]1[S:1][C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 593268134-(Benzo[d]thiazol-2-ylamino)phenolHCID 59351251HCID 59351251, compound

Product 1

HCID 59351196HCID 59351196, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
163 °C

Procedure

To a solution of 4-(benzo[d]thiazol-2-ylamino)phenol (0.094 g, 0.390 mmol) and methyl 4-(3-chloropyrazin-2-yl)tetrahydro-2H-pyran-4-carboxylate (0.1 g, 0.390 mmol) in DMSO (1 mL) was added cesium carbonate (0.254 g, 0.779 mmol). The resulting mixture was heated to 163° C. for ˜20 minutes. Reaction mixture was cooled back to 100 C and stirred overnight. Aqueous work up with multiple water and brine washes to remove DMSO and extraction with DCM. Purification by Shimadzu (phenomenex Gemini C18 5 um 100×30 mm; 254 UV; solvent A=0.1% TFA in water, solvent B=0.1% TFA in ACN; gradient run: 35% B to 80% B in 9 min; 1 min@ 80% B; flow rate=30 ml/min; 2 peaks contained mass 418: R1 =3.91 to 4.26 min; R2=5.83 to 6.36 min) to afford the product. MS (ESI, pos. ion) m/z: 419.0 (M+1). IC50 (uM) +++++.

Workup

  1. customReaction mixture
  2. temperaturewas cooled back to 100 C
  3. customto remove
  4. extractionDMSO and extraction with DCM
  5. customPurification by Shimadzu (phenomenex Gemini C18 5 um 100×30 mm; 254 UV; solvent A=0.1% TFA in water, solvent B=0.1% TFA in ACN; gradient run: 35% B to 80% B in 9 min; 1 min@ 80% B; flow rate=30 ml/min; 2 peaks contained mass 418: R1 =3.91 to 4.26 min; R2=5.83 to 6.36 min)
  6. customto afford the product

Sources & evidence

ORD record
ord-59ab6f1bbd144352b96c23ee127860d3
Source dataset
uspto-grants-2011_11
Patent number
US08053438B2

Reaction notes

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