Methanol → HCID 11256532, compound

HRID 895462Notes

Reaction equation

HRID 895462 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[C:4]([NH:14][CH2:15][CH2:16][NH:17][C:18](=[O:20])[CH3:19])[CH:3]=1.[Cl:21][CH2:22][C:23](Cl)=[O:24].CO.N1C(C)=CC=CC=1C>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[C:18]([NH:17][CH2:16][CH2:15][NH:14][C:4]1[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:7]=[C:2]([NH:1][C:23](=[O:24])[CH2:22][Cl:21])[CH:3]=1)(=[O:20])[CH3:19]

Participants

8

Reactant 4

HCID 887MethanolHCID 6577Chloroacetyl chloride3×HCID 79372,6-LutidineHCID 22378791N-{2-[(6-amino-2-phenylpyrimidin-4-yl)amino]ethyl}acetamide2×

Product 1

HCID 11256532HCID 11256532, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of amine 5 was titrated with chloroacetyl chloride with monitoring by TLC (SiO2/8:1 and 14:1 DCM:MeOH) as follows: Neat chloroacetyl chloride (0.45 mL; 5.7 mmol) was slowly added down the side of a flask immersed in an ice-water bath into a solution of aminopyrimidine 5 (1.531 g; 5.64 mmol) and 2,6-lutidine (2.0 mL; 17 mmol) in DCM (30 mL) plus DMF (2.5 mL). Starting material remained so additional chloroacetyl chloride was added after 0.4 h (0.45 μL; 5.7 mmol) and again after an additional 0.5 h (90 IL; 1.1 mmol). After 0.5 h, EtOAc (150 mL) was added and the solution washed with saturated NaHCO3 (40 mL), 50% saturated NaCl (5×40 mL), saturated NaCl (2×40 mL), dried (MgSO4), filtered and concentrated to a yellow-orange crystalline solid. The crude material was triturated with hexanes (10 mL) then 1:1 hexanes:Et2O (2×10 mL) then purified on silica gel (250 mL) with 18:1 DCM:MeOH yielding a hard yellow foam (1.78 g; 91%). LC (method B) tR=13.5 min; 1H NMR (200 MHz, CDCl3) δ 8.70 (brs, 1H), 8.35 (m, 2H), 7.47 (m, 3H), 7.16 (s, 1H), 6.48 (brs, 1H), 5.59 (brt, 1H), 4.19 (s, 2H), 3.68 (m, 2H), 3.54 (m, 2H), 1.88 (s, 3H); ESIMS 347.9/349.9 (100/32) [MH+].

Workup

  1. additionwas added after 0.4 h (0.45 μL; 5.7 mmol)
  2. waitAfter 0.5 h
  3. washthe solution washed with saturated NaHCO3 (40 mL), 50% saturated NaCl (5×40 mL), saturated NaCl (2×40 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated to a yellow-orange crystalline solid
  7. customThe crude material was triturated with hexanes (10 mL)
  8. custom1:1 hexanes:Et2O (2×10 mL) then purified on silica gel (250 mL) with 18:1 DCM

Sources & evidence

ORD record
ord-2ee899468d0644f7b848b2c8277f9f46
Source dataset
uspto-grants-2005_07
Patent number
US06916804B2

Reaction notes

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