Hydrochloric Acid → HCID 25197173, compound

HRID 2067913Notes

Reaction equation

HRID 2067913 reaction equation
[F:1][CH:2]([F:37])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([CH3:36])=[C:21]([CH:35]=3)[CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][CH:27]([C:30]([O:32]CC)=[O:31])[CH2:26][CH2:25]3)=[N:14][CH:15]=2)=[CH:6][CH:5]=1.C1COCC1.[OH-].[Li+].Cl>CO>[F:37][CH:2]([F:1])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[N:12][C:13]([NH:16][C:17]3[CH:18]=[CH:19][C:20]([CH3:36])=[C:21]([CH:35]=3)[CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][CH:27]([C:30]([OH:32])=[O:31])[CH2:26][CH2:25]3)=[N:14][CH:15]=2)=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 68726041HCID 68726041, compound

Product 1

HCID 25197173HCID 25197173, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To ethyl 1-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenethyl)piperidine-4-carboxylate 52 (0.6 mmol) is added THF (3 mL), MeOH (2 mL) and 3M lithium hydroxide (7.3 mmol). The reaction mixture is stirred at rt for 6 h until complete as detected by LCMS. Subsequently, the organic solvents are evaporated and the reaction mixture is diluted with water (10 mL) then neutralized with 3M HCl (7.3 mmol). The resulting precipitate is filtered, washed with water and air dried. The crude precipitate is purified by preparative LCMS to yield 1-(5-(5-(4-(difluoromethoxy)phenyl)pyrimidin-2-ylamino)-2-methylphenethyl)piperidine-4-carboxylic acid F2 as white solid. 1H NMR (400 MHz, d6-DMSO) δ 9.69 (s, 1H), 8.79 (s, 2H), 7.75 (d, J=8.0 Hz, 2H), 7.60 (bd, J=8.0 Hz, 1H), 7.56 (bs, 1H), 7.46 (s, 1H), 7.28 (d, J=8.0 Hz, 2H), 7.12 (d, J=8.0 Hz, 1H), 3.19 (m, 1H), 2.96 (m, 2H), 2.27 (s, 3H), 2.10 (m, 2H), 1.75 (m, 2H). MS (m/z) (M+1)+: 483.2.

Workup

  1. customSubsequently, the organic solvents are evaporated
  2. additionthe reaction mixture is diluted with water (10 mL)
  3. filtrationThe resulting precipitate is filtered
  4. washwashed with water and air
  5. customdried
  6. customThe crude precipitate is purified by preparative LCMS

Sources & evidence

ORD record
ord-217cad3e08a7443d86c856953f3cf5e1
Source dataset
uspto-grants-2012_10
Patent number
US08293757B2

Reaction notes

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