The South African cricketers remain firmly in control of the third and final test against England and the number one world ranking.
The homeside ended the 4th day at Lord's on 16 for 2, chasing 346 for an unlikely win.
Vernon Philander removed both England openers, Alistair Cook for 3 and Andrew Strauss, who is playing his 100th test, for one.
The most England have ever made in the fourth innings to win a Test is the 7-332 they posted against Australia at Melbourne back in 1928/29.
Earlier, Hashim Amla's composed 121 was the cornerstone of South Africa's second innings 351.
South Africa lead the series 1-nil and will overtake England at the top of the Test Championship if they win the series.