Dichloromethane → HSD Inhibitor 23

HRID 2276935Notes

Reaction equation

HRID 2276935 reaction equation
[CH3:1][C:2]([N:7]1[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][N:14]=2)[CH2:9][CH2:8]1)([CH3:6])[C:3](O)=[O:4].O.[OH:24][C:25]1[C:33]2N=NN[C:29]=2[CH:28]=[CH:27][CH:26]=1.Cl.CN(C)[CH2:37][CH2:38][CH2:39][N:40]=C=NCC.[CH2:46](Cl)Cl>CCN(C(C)C)C(C)C>[CH3:6][C:2]([N:7]1[CH2:8][CH2:9][N:10]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:20])([F:22])[F:21])=[CH:15][N:14]=2)[CH2:11][CH2:12]1)([C:3]([NH:40][CH:39]1[CH:27]2[CH2:26][C:25]3([OH:24])[CH2:37][CH:38]1[CH2:46][CH:29]([CH2:33]3)[CH2:28]2)=[O:4])[CH3:1]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 16100379HCID 16100379, compoundHCID 178526939HCID 178526939, compound

Product 1

HCID 11634114HSD Inhibitor 23

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Procedure

A solution of 2-methyl-2-[4-(5-trifluoromethyl-pyridin-2-yl)-piperazin-1-yl]-propionic acid (159 mg, 0.5 mmoles) from Example 14C in DCM (5 mL) and DIPEA (0.5 mL) was treated with hydroxybenzotriazole hydrate (HOBt) (84 mg, 0.6 mmoles), 5-hydroxy-2-adamantamine (100 mg, 0.6 mmoles) from Example 13A and 15 minutes later with (3-dimethylaminopropyl)-3-ethylcarbodiimide HCl (EDCI) (115 mg, 0.6 mmoles). The mixture was stirred overnight at room temperature after which the DCM was removed under reduced pressure and the residue was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic extracts washed with saturated sodium bicarbonate, water, dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure and the crude product purified (silica gel, 10-40% acetone in hexane) to provide the title compound as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.41 (s, 1H), 7.67 (m, 2H), 6.66 (d, J=9.1 Hz, 1H), 4.0 (d, J=7.8 Hz, 1H), 3.66 (m, 4H), 2.64 (m, 4H), 2.23-2.1 (m, 3H), 1.9-1.63 (m, 10H), 1.25 (s, 6H); MS (APCI+) m/z 467 (M+H)+.

Workup

  1. customwas removed under reduced pressure
  2. customthe residue was partitioned between water and ethyl acetate
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washthe combined organic extracts washed with saturated sodium bicarbonate, water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe crude product purified (silica gel, 10-40% acetone in hexane)

Sources & evidence

ORD record
ord-9ace54a6021a4c7a94de1acec28fecee
Source dataset
uspto-grants-2015_09
Patent number
US09133145B2

Reaction notes

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