Acetic Acid → HCID 11718798, compound

HRID 216112Notes

Reaction equation

HRID 216112 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[C:7]([C:9]2[S:13][C:12]([CH:14]=O)=[CH:11][CH:10]=2)[CH:6]=[C:5]([NH:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[N:4]=1.[NH:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>CO.ClCCCl.C1CCCCC1.CCOC(C)=O>[CH3:26][O:25][C:22]1[CH:21]=[CH:20][C:19]([CH2:18][CH2:17][NH:16][C:5]2[CH:6]=[C:7]([C:9]3[S:13][C:12]([CH2:14][N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)=[CH:11][CH:10]=3)[N:8]=[C:3]([O:2][CH3:1])[N:4]=2)=[CH:24][CH:23]=1

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 31268Pyrrolidine2×HCID 5049666Sodium triacetoxyborohydride2×HCID 11501553HCID 11501553, compound

Product 1

HCID 11718798HCID 11718798, compoundYield 70%

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 8078CyclohexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-{2-methoxy-6-[2-(4-methoxy-phenyl)-ethylamino]-pyrimidin-4-yl}-thiophene-2-carbaldehyde [250 mg, 0.68 mmol, Example 8(b)], pyrrolidine (170 μL, 2.03 mmol) and sodium triacetoxyborohydride (502 mg, 2.37 mmol) in MeOH (10 mL) and 1,2-dichloroethane (10 mL) is treated with acetic Acid (116 mL, 2.03 mmol) to bring the pH to 6.0, stirred at ambient temperature for 6 hours, and treated with pyrrolidine (170 μL, 2.03 mmol) and sodium triacetoxyborohydride (502 mg, 2.37 mmol). The reaction mixture is stirred at ambient temperature overnight concentrated by rotary evaporator. The residual gum is partitioned between EtOAc and saturated sodium bicarbonate solution. The organic phase is separated, dried over magnesium sulfate, filtered and concentrated to provide a solid, which is subjected to flash column chromatography on silica gel eluting with a mixture of EtOAc and cyclohexane to afford [2-(4-methoxy-phenyl)-ethyl]-[2-methoxy-6-(5-pyrrolidin-1-ylmethyl-thiophen-2-yl)-pyrimidin-4-yl]-amine [202 mg, 70%, Example 13(a)]. LCMS: RT=5.37 minutes, MS: 425 (M+H). IC50=44 nM

Workup

  1. stirringThe reaction mixture is stirred at ambient temperature overnight
  2. concentrationconcentrated by rotary evaporator
  3. customThe residual gum is partitioned between EtOAc and saturated sodium bicarbonate solution
  4. customThe organic phase is separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto provide a solid, which

Sources & evidence

ORD record
ord-6df143fa7d14472d94dce2f9cc6d4732
Source dataset
uspto-grants-2012_06
Patent number
US08193183B2

Reaction notes

Loading…