Diisopropylethylamine → HCID 90405634, compound

HRID 1505651Notes

Reaction equation

HRID 1505651 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][C@H:3]1[OH:15].Cl[C:17]1[C:18]2[CH:25]=[C:24]([CH2:26][C:27]([F:30])([F:29])[F:28])[S:23][C:19]=2[N:20]=[CH:21][N:22]=1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[CH2:8]([N:5]1[CH2:6][CH2:7][C@@H:2]([NH:1][C:17]2[C:18]3[CH:25]=[C:24]([CH2:26][C:27]([F:30])([F:29])[F:28])[S:23][C:19]=3[N:20]=[CH:21][N:22]=2)[C@H:3]([OH:15])[CH2:4]1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 13677860HCID 13677860, compoundHCID 904050864-Chloro-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine

Product 1

HCID 90405634HCID 90405634, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

The mixture of 36.7 mg of trans-4-amino-1-benzylpiperidin-3-ol (0.18 mmol), 30 mg of 4-chloro-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine (0.12 mmol) and 46 mg of N,N-diisopropylethylamine (0.36 mmol) was refluxed in 0.75 mL of isopropanol for 18 hs. Then reaction mixture was concentrated and purified on silica gel column eluting with DCM:MeOH 20:1 to afford 45 mf of trans-1-benzyl-4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-3-ol (Compound 165). Its monohydrochloride salt was obtained by adding 1 equivalent of 1N HCl solution in diethyl ether to a solution of compound in ethanol. 1H NMR (600 MHz, CD3OD) of HCl salt, signals are all broadened because of intramolecular H-bond: δ 8.37 (1H), 7.51-7.60 (6H), 4.43 (4H), 4.12 (1H), 3.85 (2H), 3.55 (2H), 3.21 (1H), 2.99 (1H), 2.06 (1H). 13C NMR (150 MHz, CD3OD): δC 165.78, 158.45, 153.97, 132.59, 131.46, 130.51, 130.18, 127.45, 125.62, 122.09, 118.50, 68.02, 61.86, 56.88, 54.15, 52.38, 35.81 (q, J=31.5 Hz), 28.14. ESI MS [MH+]: 423.1458.

Workup

  1. customThen reaction mixture
  2. concentrationwas concentrated
  3. custompurified on silica gel column
  4. washeluting with DCM:MeOH 20:1

Sources & evidence

ORD record
ord-82815d758332412e970f50eac9cdc049
Source dataset
uspto-grants-2015_12
Patent number
US09216993B2

Reaction notes

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