Piperidin-4-ol → N-(5-{5-[(4-hydroxypiperidin-1-yl)carbonyl]-2-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamide

HRID 1364489Notes

Reaction equation

HRID 1364489 reaction equation
[C:1]([NH:4][C:5]1[S:6][C:7]([C:11]2[S:15][C:14]([C:16]([OH:18])=O)=[CH:13][CH:12]=2)=[C:8]([CH3:10])[N:9]=1)(=[O:3])[CH3:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[OH:52][CH:53]1[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1.CCN(C(C)C)C(C)C>C1COCC1>[OH:52][CH:53]1[CH2:58][CH2:57][N:56]([C:16]([C:14]2[S:15][C:11]([C:7]3[S:6][C:5]([NH:4][C:1](=[O:3])[CH3:2])=[N:9][C:8]=3[CH3:10])=[CH:12][CH:13]=2)=[O:18])[CH2:55][CH2:54]1

Participants

6

Reactant 4

HCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 119933965-[2-(Acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-carboxylic acid2×

Product 1

HCID 11993490N-(5-{5-[(4-hydroxypiperidin-1-yl)carbonyl]-2-thienyl}-4-methyl-1,3-thiazol-2-yl)acetamideYield 23%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-[2-(Acetylamino)-4-methyl-1,3-thiazol-5-yl]thiophene-2-carboxylic acid, Compound (4) (50 mg; 0.18 mmol; 1 eq.), is dissolved in THF (8 ml). PyBOP (138.2 mg; 0.27 mmol; 1.50 eq.), 4-hydroxypiperidine (53.7 mg; 0.53 mmol; 3 eq.) and DIEA (0.06 ml; 0.35 mmol; 2 eq.) are added successively. The reaction mixture is stirred at room temperature for 2 hours. The solvents are evaporated and the crude product is suspended in MeCN, filtered and washed several times with MeCN, affording Compound (7) as brown solid (15.2 mg; 23%). 1H NMR (DMSO-d6) δ 1.30-1.45 (m, 2H), 1.72-1.85 (m, 2H), 2.14 (s, 3H), 2.42 (s, 3H), 3.25-3.38 (m, 2H), 3.75 (m, 1H), 3.85-4.02 (m, 2H), 4.80 (d, J=6 Hz, 1H), 7.13 (d, J=6 Hz, 1H), 7.36 (d, J=6 Hz, 1H), 12.18 (br s, 1H). M−(ESI): 364.12; M+(ESI): 366.10. HPLC, Rt: 2.35 min (purity: 97.9%).

Workup

  1. customThe solvents are evaporated
  2. filtrationfiltered
  3. washwashed several times with MeCN

Sources & evidence

ORD record
ord-a41d2db826004ea8961299e984c208c3
Source dataset
uspto-grants-2011_02
Patent number
US07888379B2

Reaction notes

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