Hydrochloric Acid → HCID 70945137, compound

HRID 525085Notes

Reaction equation

HRID 525085 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]1[C:18]2[C:17]([O:19][CH:20]3[CH2:25][CH2:24][CH:23]([N:26](C)[C:27](=O)OC(C)(C)C)[CH2:22][CH2:21]3)=[N:16][CH:15]=[N:14][C:13]=2[S:12][CH:11]=1.Cl.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[O:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]1[C:18]2[C:17]([O:19][CH:20]3[CH2:21][CH2:22][CH:23]([NH:26][CH3:27])[CH2:24][CH2:25]3)=[N:16][CH:15]=[N:14][C:13]=2[S:12][CH:11]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 68110057HCID 68110057, compound

Product 1

HCID 70945137HCID 70945137, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl N-(4-[[5-(1-benzofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]cyclohexyl)-N-methylcarbamate (60 mg, 0.13 mmol, 1.00 equiv) in dichloromethane (5 mL) was added hydrochloric acid (1 mL, 12 M) at 0° C. and stirred for 1 h at room temperature. The pH value of the solution was adjusted to 9 with sodium carbonate (sat.) and extracted with 3×20 mL of dichloromethane. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum to give 40 mg (84%) of 4-[[5-(1-benzofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]-N-methylcyclohexan-1-amine as colorless oil which was used directly for next step. To a solution of 4-[[5-(1-benzofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]-N-methylcyclohexan-1-amine (40 mg, 0.11 mmol, 1.00 equiv) in methanol (2 mL) was added HCHO (37%, 0.07 mL, 1.06 mmol) and stirred for 1 h at room temperature. Then NaBH3CN (20 mg, 0.32 mmol, 3.01 equiv) was added and stirred for additional 1 h at room temperature. The reaction was then quenched by the addition of 20 mL of NH4Cl (sat.) and extracted with 3×20 mL of ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated under vacuum. The crude product (60 mg) was re-crystallized from ethyl acetate to give 15 mg (36%) of pure 4-[[5-(1-benzofuran-2-yl)thieno[2,3-d]pyrimidin-4-yl]oxy]-N,N-dimethylcyclohexan-1-amine as a white solid. MS (ES, m/z): 394 [M+H]+. 1H NMR (300 MHz, CD3OD): δ 8.66 (s, 1H), 8.08 (s, 1H), 7.68-7.65 (d, 1H), 7.56-7.54 (d, 1H), 7.38-7.25 (m, 3H), 5.45-5.42 (m, 1H), 3.33 (s, 1H), 2.90 (s, 6H), 2.53-2.50 (d, 2H), 2.23-2.20 (d, 2H), 1.82-1.66 (m, 4 H).

Workup

  1. extractionextracted with 3×20 mL of dichloromethane
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-62b35bfc77664de6b27be6702dfcfbd5
Source dataset
uspto-grants-2016_05
Patent number
US09340554B2

Reaction notes

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