Diisopropylethylamine → HCID 178490987, compound

HRID 2200885Notes

Reaction equation

HRID 2200885 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]([OH:26])=O)=[CH:9][N:8]=1)[CH2:2]2.[OH:27][C@H:28]1[CH2:33][CH2:32][C@H:31]([NH2:34])[CH2:30][CH2:29]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>C1COCC1>[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]([NH:34][C@H:31]3[CH2:32][CH2:33][C@H:28]([OH:27])[CH2:29][CH2:30]3)=[O:26])=[CH:9][N:8]=1)[CH2:2]2

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 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 acidHCID 178511715HCID 178511715, compound

Product 1

HCID 178490987HCID 178490987, compoundYield 62.2%

Reagents, catalysts & solvents 1

HCID 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 (180 mg, 0.48 mmol), trans-4-hydroxycyclohexylamine (66 mg, 0.58 mmol) and HATU (220 mg, 0.58 mmol). The solution was cooled in an ice bath and DIEA (0.25 mL, 1.44 mmol) was added then. The reaction was conducted at ambient temperature for 8 h, followed by concentration, addition of water and extraction with ethyl acetate. The organic phase was dried, concentrated and purified by silica gel column chromatography (DCM/methanol=20/1) to give 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-chloro-4-methoxybenzyl)amino)-N-(trans-4-hydroxycyclohexanyl)pyrimidine-5-formamide (141 mg, 62% yield).

Workup

  1. temperatureThe solution was cooled in an ice bath
  2. concentrationfollowed by concentration, addition of water and extraction with ethyl acetate
  3. customThe organic phase was dried
  4. concentrationconcentrated
  5. custompurified by silica gel column chromatography (DCM/methanol=20/1)

Sources & evidence

ORD record
ord-89712f0682724e54ab5f354714b2822d
Source dataset
uspto-grants-2016_06
Patent number
US09359371B2

Reaction notes

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