Trifluoroacetic acid → HCID 73214322, compound

HRID 2200880Notes

Reaction equation

HRID 2200880 reaction equation
[CH:1]12[CH2:6][CH:5]1[CH2:4][N:3]([C:7]1[N:12]=[C:11]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=3)[C:10]([C:24](O)=[O:25])=[CH:9][N:8]=1)[CH2:2]2.[NH2:27][CH2:28][CH:29]1[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>C1COCC1.C(Cl)Cl>[CH:5]12[CH2:6][CH:1]1[CH2:2][N:3]([C:7]1[N:12]=[C:11]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([Cl:23])[CH:16]=3)[C:10]([C:24]([NH:27][CH2:28][CH:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[O:25])=[CH:9][N:8]=1)[CH2:4]2

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 7368171-Boc-4-(aminomethyl)piperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1176225452-(3-Azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acid

Product 1

HCID 73214322HCID 73214322, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In THF (20 mL) were dissolved 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-pyrimidine-5-carboxylic acid (150 mg, 0.40 mmol), tert-butyl 4-(aminomethyl)piperidine-1-carboxylate (128 mg, 0.60 mmol) and HATU (182 mg, 0.48 mmol). DIEA (0.20 mL, 1.2 mmol) was added dropwisely. The reaction was conducted at ambient temperature for 8 h. The reaction mixture was concentrated, followed by addition of water and extraction with DCM. The organic phase was dried, concentrated, and purified by silica gel column chromatography (DCM/methanol=50/1) to give a white solid. The product was dissolved in DCM (10 mL), and trifluoroacetic acid (1 mL) was added. The reaction was conducted at ambient temperature for 4 h. Then the reaction mixture was adjusted to a pH of 9 with saturated aqueous sodium bicarbonate. The organic phase was dried and the solvent was removed by rotary evaporation to give 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(piperdin-4-ylmethyl)pyrimidine-5-formamide (34 mg, 18% yield).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additionfollowed by addition of water and extraction with DCM
  3. customThe organic phase was dried
  4. concentrationconcentrated
  5. custompurified by silica gel column chromatography (DCM/methanol=50/1)
  6. customto give a white solid
  7. waitThe reaction was conducted at ambient temperature for 4 h
  8. customThe organic phase was dried
  9. customthe solvent was removed by rotary evaporation

Sources & evidence

ORD record
ord-470f3db7b1ea4624948d155e3eae547c
Source dataset
uspto-grants-2016_06
Patent number
US09359371B2

Reaction notes

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