1-Hydroxybenzotriazole → (R)-tert-butyl 2-((6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinamido)methyl)pyrrolidine-1-carboxylate

HRID 2080283Notes

Reaction equation

HRID 2080283 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:17]=[CH:16][C:12]([C:13](O)=[O:14])=[C:11]([NH:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=2)[N:10]=1)#[N:2].[NH2:28][CH2:29][C@H:30]1[CH2:34][CH2:33][CH2:32][N:31]1[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36].C1C=CC2N(O)N=NC=2C=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:17]=[CH:16][C:12]([C:13]([NH:28][CH2:29][C@H:30]2[CH2:34][CH2:33][CH2:32][N:31]2[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[O:14])=[C:11]([NH:18][CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([F:27])[CH:22]=2)[N:10]=1)#[N:2]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 1512534tert-butyl (2R)-2-(aminomethyl)pyrrolidine-1-carboxylateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 575423046-(2-Cyanophenyl)-2-(3-fluorophenethylamino)nicotinic acid

Product 1

HCID 57543030(R)-tert-butyl 2-((6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinamido)methyl)pyrrolidine-1-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinic acid (510 mg, 1.41 mmol), (R)-tert-butyl 2-(aminomethyl)pyrrolidine-1-carboxylate (424 mg, 2.11 mmol), HOBT (285 mg, 2.11 mmol), and HBTU (800 mg, 2.11 mg) in RB flask was added DMF and the mixture was stirred at r.t. for 1 h. LC/MS indicated the reaction was complete and the mixture was filtered and purified on RP-HPLC using a mixture of acetonitrile and water to give (R)-tert-butyl 2-((6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinamido)methyl)pyrrolidine-1-carboxylate (695.1 mg, 91%). LRMS (M+H+) m/z 544.2.

Workup

  1. filtrationthe mixture was filtered
  2. custompurified on RP-HPLC
  3. additiona mixture of acetonitrile and water

Sources & evidence

ORD record
ord-c4de64ba5339450c98dbe1e830d07f53
Source dataset
uspto-grants-2011_04
Patent number
US07932270B2

Reaction notes

Loading…