Ammonium Chloride → 4-((1R,3S)-3-Hydroxycyclohexylamino)-2-(methylthio)pyrimidine-5-carboxamide

HRID 2280728Notes

Reaction equation

HRID 2280728 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9]2[C:14]([C:15](O)=[O:16])=[CH:13][N:12]=[C:11]([S:18][CH3:19])[N:10]=2)[CH2:3]1.C[N:21](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl-].[NH4+].CCN(C(C)C)C(C)C>CN(C=O)C>[OH:1][C@H:2]1[CH2:7][CH2:6][CH2:5][C@@H:4]([NH:8][C:9]2[C:14]([C:15]([NH2:21])=[O:16])=[CH:13][N:12]=[C:11]([S:18][CH3:19])[N:10]=2)[CH2:3]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 712368824-((1R,3S)-3-Hydroxycyclohexylamino)-2-(methylthio)pyrimidine-5-carboxylic acid

Product 1

HCID 712372644-((1R,3S)-3-Hydroxycyclohexylamino)-2-(methylthio)pyrimidine-5-carboxamideYield 93.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-((1R,3S)-3-hydroxycyclohexylamino)-2-(methylthio)pyrimidine-5-carboxylic acid (4.5 g, 15.88 mmol) and HATU (9.06 g, 23.82 mmol) were dissolved in DMF (75 ml) and allowed to stir for 5 min at room temperature before adding ammonium chloride (4.25 g, 79 mmol) and DIEA (13.87 ml, 79 mmol). The reaction turned yellow upon addition of the base. The reaction was allowed to stir at room temperature for 1 h then partitioned between water and ethyl acetate. The organic layer was washed once with brine before drying over sodium sulfate, filtering, and concentrating to afford 4-((1R,3S)-3-hydroxycyclohexylamino)-2-(methylthio)pyrimidine-5-carboxamide (4.19 g, 14.84 mmol, 93% yield) as an off-white solid. MS (ESI) m/z 283.2 [M+1]+.

Workup

  1. additionThe reaction turned yellow upon addition of the base
  2. stirringto stir at room temperature for 1 h
  3. customthen partitioned between water and ethyl acetate
  4. washThe organic layer was washed once with brine
  5. dry with materialbefore drying over sodium sulfate
  6. filtrationfiltering
  7. concentrationconcentrating

Sources & evidence

ORD record
ord-944fa76d2913422b95bd436caf9d0125
Source dataset
uspto-grants-2015_09
Patent number
US09139534B2

Reaction notes

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