5-(2-methylsulfonyl-pyrimidin-4-yl)-thiophene-2sulfonic acid [1-(3-cyanobenzyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide → 5-(2-amino-pyrimidin-4-yl)-thiophene-2-sulfonic acid [1-(3-cyanobenzyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide

HRID 2768Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][CH:33]=1)[CH2:6][N:7]1[CH2:11][CH2:10][C@H:9]([NH:12][S:13]([C:16]2[S:17][C:18]([C:21]3[CH:26]=[CH:25][N:24]=[C:23](S(C)=O)[N:22]=3)=[CH:19][CH:20]=2)(=[O:15])=[O:14])[C:8]1=[O:30])#[N:2].C(C1C=C(C=CC=1)CN1CC[C@H](NS(C2SC(C3C=CN=C(S(C)(=O)=O)N=3)=CC=2)(=O)=O)C1=O)#[N:35]>CCO>[C:1]([C:3]1[CH:4]=[C:5]([CH:31]=[CH:32][CH:33]=1)[CH2:6][N:7]1[CH2:11][CH2:10][C@H:9]([NH:12][S:13]([C:16]2[S:17][C:18]([C:21]3[CH:26]=[CH:25][N:24]=[C:23]([NH2:35])[N:22]=3)=[CH:19][CH:20]=2)(=[O:15])=[O:14])[C:8]1=[O:30])#[N:2]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of [5-(2-methylsulfinyl-pyrimidin-4-yl)-thiophene-2-sulfonic acid [1-(3-cyanobenzyl)-2-oxo-pyrrolidin3-(S)-yl]-amide and [5-(2-methylsulfonyl-pyrimidin-4-yl)-thiophene-2sulfonic acid [1-(3-cyanobenzyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide (0.20 g, 0.39 mmol) is dissolved in 10 mL of EtOH and NH3 gas is bubbled through the solution for 5 min. The resulting mixture is heated at 90° C. for 3 h in a stainless steel Parr high pressure reaction vessel. After this time, the solution is allowed to cool to room temperature and is concentrated in vacuo to give [5-(2-amino-pyrimidin-4-yl)-thiophene-2-sulfonic acid [1-(3-cyanobenzyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide (0.20 g) as a crude product. FAB MS, [M+H]+ =455. The crude [5-(2-amino-pyrimidin-4-yl)-thiophene-2-sulfonic acid [1-(3-cyanobenzyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide is converted to the title compound as described in EXAMPLE 1, Part F. The crude product is purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 60% CH3CN/H2O (0.1% TFA) and the appropriate product fractions are lyophilized to provide the title compound as a white solid.

Workup

customNH3 gas is bubbled through the solution for 5 min
temperatureto cool to room temperature
concentrationis concentrated in vacuo

Sources & evidence

ORD record: ord-60b484981a1542b5a69074c8e93eaa5c
Source dataset: uspto-grants-1998_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05731315

Reaction notes

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