1-Hydroxybenzotriazole → Tert-butyl 4-(2-((6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamate

HRID 2080285Notes

Reaction equation

HRID 2080285 reaction equation
Cl.[C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[CH:24]=[CH:23][C:13]([C:14]([NH:16][CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][NH:19]2)=[O:15])=[C:12]([NH:25][CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=2)[N:11]=1)#[N:3].[C:35]([O:39][C:40]([NH:42][CH2:43][CH2:44][CH2:45][C:46](O)=[O:47])=[O:41])([CH3:38])([CH3:37])[CH3:36].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.CCN(C(C)C)C(C)C>CN(C=O)C>[C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[CH:24]=[CH:23][C:13]([C:14]([NH:16][CH2:17][CH:18]2[CH2:22][CH2:21][CH2:20][N:19]2[C:46](=[O:47])[CH2:45][CH2:44][CH2:43][NH:42][C:40](=[O:41])[O:39][C:35]([CH3:36])([CH3:38])[CH3:37])=[O:15])=[C:12]([NH:25][CH2:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[CH:29]=2)[N:11]=1)#[N:3]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2948944-(((Tert-butoxy)carbonyl)amino)butanoic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67101158HCID 67101158, compound

Product 1

HCID 57542726Tert-butyl 4-(2-((6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamateYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 6-(2-cyanophenyl)-2-(3-fluorophenethylamino)-N-(pyrrolidin-2-ylmethyl)nicotinamide hydrochloride (95 mg, 0.2 mmol), 4-(tert-butoxycarbonylamino)butanoic acid (61 mg, 0.3 mmol), HOBT (41 mg, 0.3 mmol), and HBTU (114 mg, 0.3 mmol) were added DMF (1.0 mL) and DIEA (0.1 mL, 0.6 mmol). The reaction mixture was stirred at r.t. for 1 h. LC/MS indicated the reaction was complete. The reaction mixture was then filtered and the filtrate was purified on RP-HPLC using a mixture of acetonitrile and water to give tert-butyl 4-(2-((6-(2-cyanophenyl)-2-(3-fluorophenethylamino)nicotinamido)methyl)pyrrolidin-1-yl)-4-oxobutylcarbamate (81.2 mg, 65%). LRMS (M+H+) m/z 629.2.

Workup

  1. filtrationThe reaction mixture was then filtered
  2. customthe filtrate was purified on RP-HPLC
  3. additiona mixture of acetonitrile and water

Sources & evidence

ORD record
ord-07140d22ddf74e77983fa96bd6a68676
Source dataset
uspto-grants-2011_04
Patent number
US07932270B2

Reaction notes

Loading…