4-Hydroxybenzaldehyde → 4-((4-((6-(2,2,2-Trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)phenol

HRID 1505646Notes

Reaction equation

HRID 1505646 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8]2[C:9]3[CH:16]=[C:15]([CH2:17][C:18]([F:21])([F:20])[F:19])[S:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH2:3][CH2:2]1.[OH:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1.[BH3-]C#N.[Na+]>CO.C(O)(=O)C>[F:20][C:18]([F:21])([F:19])[CH2:17][C:15]1[S:14][C:10]2[N:11]=[CH:12][N:13]=[C:8]([NH:7][CH:4]3[CH2:5][CH2:6][N:1]([CH2:27][C:26]4[CH:29]=[CH:30][C:23]([OH:22])=[CH:24][CH:25]=4)[CH2:2][CH2:3]3)[C:9]=2[CH:16]=1

Participants

6

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 90404759N-(piperidin-4-yl)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-amine

Product 1

HCID 862960894-((4-((6-(2,2,2-Trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)phenol

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Procedure

59 mg of N-(piperidin-4-yl)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-amine (0.19 mmol) and 21 mg of p-hydroxybenzaldehyde (0.19 mmol) were dissolved in 0.5 mL of MeOH in the presence of 10 uL of acetic acid. 19 mg of NaBH3CN (0.3 mmol) was slowly added to that mixture and solution was stirred for 24 hs. All volatiles were removed under reduced pressure and residue was partitioned between water and ethyl acetate. Organic layer was washed with brine, dried over magnesium sulfate and evaporated. The residue was purified on silica gel column with DCM:MeOH:Et3N as eluent resulting in 62 mg of 4-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)phenol (compound 105). 1H NMR (600 MHz, CDCl3): δ 8.46 (s, 1H), 7.09 (d, 2H, J=8.4 Hz), 7.07 (s, 1H), 6.68 (d, 2H, J=8.4 Hz), 5.28 (d, 1H, J=7.7 Hz), 4.21 (m, 1H), 3.59 (q, 2H, 9.9 Hz), 3.46 (s, 2H), 2.96 (m, 2H), 2.21 (m, 2H), 2.09 (m, 2H), 1.62 (m, 2H). 13C NMR (150 MHz, CDCl3): δC 166.45, 156.08, 155.98, 154.14, 131.01, 128.23, 125.57, 118.65, 116.52, 115.62, 62.48, 52.10, 47.96, 35.50 (q, J=31.5 Hz), 31.89. ESI MS [MH+]: 423.1458. Its monohydrochloride salt was obtained by adding 1 equivalent of 1N HCl solution in diethyl ether to a solution of compound in ethanol.

Workup

  1. customAll volatiles were removed under reduced pressure and residue
  2. customwas partitioned between water and ethyl acetate
  3. washOrganic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. customevaporated
  6. customThe residue was purified on silica gel column with DCM

Sources & evidence

ORD record
ord-3cffd377b6094c368f3a5f94d6762b01
Source dataset
uspto-grants-2015_12
Patent number
US09216993B2

Reaction notes

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