Dichloromethane → HCID 178490988, compound

HRID 2200906Notes

Reaction equation

HRID 2200906 reaction equation
C(Cl)Cl.[CH:4]12[CH2:9][CH:8]1[CH2:7][N:6]([C:10]1[N:15]=[C:14]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([F:26])[CH:19]=3)[C:13]([C:27]([OH:29])=O)=[CH:12][N:11]=1)[CH2:5]2.[OH:30][C@H:31]1[CH2:36][CH2:35][C@H:34]([NH2:37])[CH2:33][CH2:32]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C1COCC1>[CH:4]12[CH2:9][CH:8]1[CH2:7][N:6]([C:10]1[N:15]=[C:14]([NH:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([F:26])[CH:19]=3)[C:13]([C:27]([NH:37][C@H:34]3[CH2:35][CH2:36][C@H:31]([OH:30])[CH2:32][CH2:33]3)=[O:29])=[CH:12][N:11]=1)[CH2:5]2

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 1181574972-(3-Azabicyclo[3.1.0]hexan-3-yl)-4-((3-fluoro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acidHCID 178511715HCID 178511715, compound

Product 1

HCID 178490988HCID 178490988, compoundYield 27.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In the mixture of DCM (20 mL) and THF (20 mL) were dissolved 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-fluoro-4-methoxybenzyl)amino)pyrimidine-5-carboxylic acid (580 mg, 1.62 mmol), trans-4-hydroxycyclohexylamine (187 mg, 1.62 mmol), TEA (485 mg, 4.79 mmol) and HATU (2-(7-azobenzotriazole)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (743 mg, 1.95 mmol). The reaction was conducted at ambient temperature for 17 h. The solvent was removed by evaporation, followed by addition of water and extraction with DCM. The organic phase was dried over sodium sulfate and concentrated to give a solid, which was purified by silica gel column chromatography (DCM/methanol=50/1) to give 2-(3-azabicyclo[3.1.0]hexan-3-yl)-4-((3-fluoro-4-methoxybenzyl)amino)-N-(trans-4-hydroxycyclohexyl)pyrimidine-5-formamide as a faint yellow solid (200 mg, 27.1% yield).

Workup

  1. customThe solvent was removed by evaporation
  2. additionfollowed by addition of water and extraction with DCM
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customto give a solid, which
  6. customwas purified by silica gel column chromatography (DCM/methanol=50/1)

Sources & evidence

ORD record
ord-8a2fd5cfc96d4701841733d29080caac
Source dataset
uspto-grants-2016_06
Patent number
US09359371B2

Reaction notes

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