HCID 178462364, compound → HCID 178462236, compound

HRID 711965Notes

Reaction equation

HRID 711965 reaction equation
[C:1]([CH2:3][CH2:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([NH:11][C:12]2[C:17]([NH:18][C:19](=O)[C@H:20]([OH:22])[CH3:21])=[CH:16][N:15]=[C:14]3[CH:24]=[CH:25][S:26][C:13]=23)[CH2:7][CH2:6]1)#[N:2]>C(O)(=O)C>[OH:22][C@@H:20]([C:19]1[N:11]([C@H:8]2[CH2:9][CH2:10][C@H:5]([CH2:4][CH2:3][C:1]#[N:2])[CH2:6][CH2:7]2)[C:12]2=[C:13]3[S:26][CH:25]=[CH:24][C:14]3=[N:15][CH:16]=[C:17]2[N:18]=1)[CH3:21]

Participants

3

Reactant 1

HCID 178462364HCID 178462364, compound

Product 1

HCID 178462236HCID 178462236, compoundYield 10%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a mixture of 3-{trans-4-[(6-aminothieno[3,2-b]pyridin-7-yl)amino]cyclohexyl}propanenitrile (0.048 g, 0.16 mmol) and (R)-2-hydroxypropanoic acid (0.019 g, 0.21 mmol) in methylene chloride (0.96 mL) was added N,N-diisopropylethylamine (60 μL, 0.35 mmol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (66 mg, 0.17 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was washed with water. The organic layers were concentrated and purified on silica gel (eluting with 0 to 10% MeOH in dichloromethane) to give (2R)—N-(7-{[trans-4-(2-Cyanoethyl)cyclohexyl]amino}thieno[3,2-b]pyridin-6-yl)-2-hydroxypropanamide. LCMS calculated for C19H25N4O2S (M+H)+: m/z=373.2. Found: 373.0. A solution of the amide intermediate in acetic acid (0.3 mL) was stirred at 105° C. for 5 h. The solvent in the reaction mixture was removed in vacuo, diluted with MeOH and purified on 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 the desired product (6 mg, 10%). LCMS calculated for C19H23N4OS (M+H)+: m/z=355.2. Found: 355.1.

Workup

  1. customThe solvent in the reaction mixture was removed in vacuo
  2. additiondiluted with MeOH
  3. custompurified on RP-HPLC (XBridge C18 column
  4. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Sources & evidence

ORD record
ord-8de3c4afc0044b6cadb616a1132f29bc
Source dataset
uspto-grants-2015_11
Patent number
US09181271B2

Reaction notes

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