Triethylamine → HCID 73774918, compound

HRID 712106Notes

Reaction equation

HRID 712106 reaction equation
O[CH:2]([C:4]1[N:15]([C@@H:16]2[CH2:21][O:20][C@@H:19]([CH2:22][C:23]#[N:24])[CH2:18][CH2:17]2)[C:7]2=[C:8]3[S:14][CH:13]=[CH:12][C:9]3=[N:10][CH:11]=[C:6]2[N:5]=1)[CH3:3].[CH2:25]([N:27](CC)CC)C.CS(Cl)(=O)=O.[Cl-].C[NH3+]>C(Cl)Cl>[CH3:25][NH:27][CH:2]([C:4]1[N:15]([C@@H:16]2[CH2:21][O:20][C@@H:19]([CH2:22][C:23]#[N:24])[CH2:18][CH2:17]2)[C:7]2=[C:8]3[S:14][CH:13]=[CH:12][C:9]3=[N:10][CH:11]=[C:6]2[N:5]=1)[CH3:3]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 11637Methanamine, hydrochloride (1:1)HCID 31297Methanesulfonyl chlorideHCID 86717559HCID 86717559, compound

Product 1

HCID 73774918HCID 73774918, compoundYield 19.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a cooled mixture of {(2R,5S)-5-[2-(1-hydroxyethyl)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-1-yl]tetrahydro-2H-pyran-2-yl}acetonitrile (10.1 mg, 0.0295 mmol) and triethylamine (12 μL, 0.088 mmol) in methylene chloride (0.18 mL) was added methanesulfonyl chloride (2.7 μL, 0.035 mmol). The resulting mixture was allowed to warm to room temperature and stirred overnight. The mixture was diluted with dichloromethane and washed with water (2×). The layers were separated and the organic concentrated. To the concentrate was added methylene chloride (0.2 mL), triethylamine (18 μL), and methylammonium chloride (6.0 mg, 0.088 mmol). The resulting mixture was stirred at room temperature over the weekend (64 h) then heated to 40° C. for 3 h. The mixture was concentrated then purified using RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give 2 mg (19%) of the desired product. LCMS calculated for C18H22N5OS (M+H)+: m/z=356.2. Found: 356.1.

Workup

  1. washwashed with water (2×)
  2. customThe layers were separated
  3. stirringThe resulting mixture was stirred at room temperature over the weekend (64 h)
  4. temperaturethen heated to 40° C. for 3 h
  5. concentrationThe mixture was concentrated
  6. customthen purified
  7. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-842f8b52a26b4fe4bc3128a3d67e56e1
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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