2-Chloro-1,1,1-triethoxyethane → HCID 178511082, compound

HRID 711995Notes

Reaction equation

HRID 711995 reaction equation
[NH2:1][C:2]1[C:3]([NH:11][C@H:12]2[CH2:17][CH2:16][C@H:15]([CH2:18][C:19]#[N:20])[CH2:14][CH2:13]2)=[C:4]2[S:10][CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[Cl:21][CH2:22][C:23](OCC)(OCC)OCC>C(O)(=O)C>[Cl:21][CH2:22][C:23]1[N:11]([C@H:12]2[CH2:13][CH2:14][C@H:15]([CH2:18][C:19]#[N:20])[CH2:16][CH2:17]2)[C:3]2=[C:4]3[S:10][CH:9]=[CH:8][C:5]3=[N:6][CH:7]=[C:2]2[N:1]=1

Participants

4

Reactant 2

HCID 3059222-Chloro-1,1,1-triethoxyethaneHCID 178511084HCID 178511084, compound

Product 1

HCID 178511082HCID 178511082, compoundYield 35.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of {trans-4-[(6-aminothieno[3,2-b]pyridin-7-yl)amino]cyclohexyl}acetonitrile (51.9 mg, 0.181 mmol) (Example 2, Step 4) and 2-chloro-1,1,1-triethoxyethane (from Aldrich, 0.105 mL, 0.549 mmol) in acetic acid (0.5 mL) was stirred at 120° C. for 30 min. The solvent was removed and the resultant residue dissolved in dichloromethane and purified on silica gel (eluting with 0-5% MeOH in dichloromethane) to give 22 mg (35.5%) of {trans-4-[2-(Chloromethyl)-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-1-yl]cyclohexyl}acetonitrile. LCMS calculated for C17H18ClN4S (M+H)+: m/z=345.1. Found: 345.0. Also eluted was 8 mg (12%) of {1-[trans-4-(cyanomethyl)cyclohexyl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl}methyl acetate, LCMS calculated for C19H21N4O2S (M+H)+: m/z=369.1. Found: 369.0. The acetate compound was treated with lithium hydroxide to give compound the desired product after HPLC purification (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min). LCMS calculated for C17H19N4OS (M+H)+: m/z=327.1. Found: 327.1. 1H NMR (500 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.01 (d, J=5.5 Hz, 1H), 7.67 (d, J=5.5 Hz, 1H), 5.80 (t, J=5.6 Hz, 1H), 4.85 (d, J=5.3 Hz, 2H), 4.74 (m, 1H), 2.61 (d, J=6.1 Hz, 2H), 2.42 (m, 2H), 2.09-1.99 (m, 5H), 1.41 (m, 2H) ppm.

Workup

  1. customThe solvent was removed
  2. dissolutionthe resultant residue dissolved in dichloromethane
  3. custompurified on silica gel (eluting with 0-5% MeOH in dichloromethane)

Sources & evidence

ORD record
ord-d224cf34536d4c85a5e5f45be530f951
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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