Sodium hydride → N-Acetyl-D-thioproline O-(2-chloropyrimidin-4-yl)-L-tyrosine methyl ester

HRID 1530937Notes

Reaction equation

HRID 1530937 reaction equation
[C:1]([N:4]1[CH2:11][S:10][CH2:9][C@@H:5]1[C:6]([OH:8])=[O:7])(=[O:3])[CH3:2].[CH3:12][O:13][C:14](=[O:25])[C@H:15]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[CH:20][CH:19]=1)[NH2:16].C(N1CSC[C@@H]1C(O)=O)(=O)C.COC(=O)[C@H](CC1C=CC(O)=CC=1)N.[H-].[Na+].[Cl:53][C:54]1[N:59]=[C:58](Cl)[CH:57]=[CH:56][N:55]=1>CN(C=O)C.O>[C:1]([N:4]1[CH2:11][S:10][CH2:9][C@@H:5]1[C:6]([OH:8])=[O:7])(=[O:3])[CH3:2].[CH3:12][O:13][C:14](=[O:25])[C@H:15]([CH2:17][C:18]1[CH:19]=[CH:20][C:21]([O:24][C:56]2[CH:57]=[CH:58][N:59]=[C:54]([Cl:53])[N:55]=2)=[CH:22][CH:23]=1)[NH2:16]

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 70652Tyrosine Methyl EsterHCID 775312,4-DichloropyrimidineHCID 749158(4S)-3-acetyl-1,3-thiazolidine-4-carboxylic acidHCID 131721907N-Acetyl-D-thioproline L-tyrosine methyl ester

Product 1

HCID 131722409N-Acetyl-D-thioproline O-(2-chloropyrimidin-4-yl)-L-tyrosine methyl esterYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Procedure

A solution of N-acetyl-D-thioproline-L-tyrosine methyl ester (1.76 g, 5 mmol), [prepared from N-acetyl-D-thioproline and tyrosine methyl ester by a similar method to the preparation of Intermediate 5] in DMF (10 ml) was added to a suspension of sodium hydride (60% in mineral oil, 210 mg, 5.25 mmol) in DMF (5 ml) at room temperature. After 10 min a solution of 2,4-dichloropyrimidine (782 mg, 5.25 mmol) in DMF (5 ml) was added. After 1 h water (1 ml) was added and the solvent evaporated in vacuo. The residue was dissolved in EtOAc (200 ml) and washed with water (3×50 ml) and brine (30 ml), dried (Na2SO4) and evaporated in vacuo. Chromatography (SiO2, MeOH/DCM 5:95) gave the title compound as a white foam (1.59 g, 68%). δH (DMSO-d6, 400K) 8.56 (1 H, d, J 5.7 Hz, PyrH), 7.9 (1 H, br d, CONH),7.32 (2 H, d,J 8.7 Hz, ArH), 7.15 (2 H, d, J 8.7 Hz, ArH), 6.99 (1 H, d, J 5.7 Hz, PyrH), 4.83 (1 H, dd, J 7.4, 3.9 Hz, CHαthiopro), 4.77 (1 H, d, J 9.2 Hz, NCHHBS), 4.64 (1 H,dt, J 8.5, 5.6 Hz, CHαtyr),4.39 (1 H, d, J 9.2 Hz, NCHAHBS), 3.67 (3 H, s, CO2Me), 3.26 (1 H, dd, J 11.6, 7.4 Hz, CHCHAHBS), 3.19 (1 H, dd, J 14.0, 5.7 Hz, CHCHAHBAr), 3.09-3.00 (2 H, m, CHCHAHBS+CHCHAHBAr) and 2.00 (3 H, s,COCH3); m/z (ESI, 15 V) 465 (MH+).

Workup

  1. customthe solvent evaporated in vacuo
  2. dissolutionThe residue was dissolved in EtOAc (200 ml)
  3. washwashed with water (3×50 ml) and brine (30 ml)
  4. dry with materialdried (Na2SO4)
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-2b008173767f4712b726a885acd7def4
Source dataset
uspto-grants-2001_03
Patent number
US06197794B1

Reaction notes

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