1-Hydroxybenzotriazole → 4-[2-(Biphenyl-4-ylcarbamoyl)-acetyl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 1665595Notes

Reaction equation

C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[C:20]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:32])[CH2:28][C:29]([OH:31])=O)=[CH:22][CH:21]=1.CCN=C=NCCCN(C)C.Cl.[C:51]([O:55][C:56]([N:58]1[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]1)=[O:57])([CH3:54])([CH3:53])[CH3:52]>CN(C=O)C.O>[C:51]([O:55][C:56]([N:58]1[CH2:63][CH2:62][N:61]([C:29](=[O:31])[CH2:28][C:27](=[O:32])[NH:26][C:23]2[CH:22]=[CH:21][C:20]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[CH:25][CH:24]=2)[CH2:60][CH2:59]1)=[O:57])([CH3:54])([CH3:52])[CH3:53]

Participants

Conditions

Temperature: 10 °C

Procedure

HOBt (570 mg, 4.2 mmol) and DIPEA (541 mg, 4.2 mmol) were added to a stirred solution of N-biphenyl-4-yl-malonamic acid (1 g, 3.5 mmol) in DMF (10 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (810 mg, 4.2 mmol) followed by piperazine-1-carboxylic acid tert-butyl ester (720 mg, 3.86 mmol) were added. The resulting reaction mixture was stirred at room temperature overnight. Water was then added and the resulting precipitate was filtered and dried to afford 1.4 g (93%) of 4-[2-(biphenyl-4-ylcarbamoyl)-acetyl]-piperazine-1-carboxylic acid tert-butyl ester. 1H NMR: (CDCl3): δ 8.6 (s, 1H), 7.9 (m, 2H), 7.7 (m, 2H), 7.65 (m, 1H), 7.5 (m, 3H), 7.4 (s, 1H), 4.1 (m, 2H), 3.6 (m, 4H), 3.4 (m, 2H), 3.1 (m, 2H).

Workup

additionwere added
customThe resulting reaction mixture
filtrationthe resulting precipitate was filtered
customdried

Sources & evidence

ORD record: ord-3061fce965ca4b658210f52ccfc56fb6
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08039463B2

Reaction notes

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