Diisopropylethylamine → Terephthalamide

HRID 906057Notes

Reaction equation

HRID 906057 reaction equation
C([N:4](CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[NH2:34][C:35]([C:37]1[CH:45]=[CH:44][C:40]([C:41](O)=[O:42])=[CH:39][C:38]=1NCC1CC1)=[O:36]>CN(C)C=O.CO>[C:37]1([C:35]([NH2:34])=[O:36])[CH:45]=[CH:44][C:40]([C:41]([NH2:4])=[O:42])=[CH:39][CH:38]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 577482454-(Aminocarbonyl)-3-[(cyclopropylmethyl)amino]benzoic acid

Product 1

HCID 76381Terephthalamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

N,N-Diisopropylethylamine (101 uL, 0.66 mmol) was added to a mixture of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (53 mg, 0.14 mmol), and 4-(aminocarbonyl)-3-[(cyclopropylmethyl)amino]-benzoic acid (synthesized according to reagent preparation 39) (31 mg, 0.13 mmol) and the resulting mixture was stirred at room temperature for 30 minutes. A solution of 1-[6-(3-endo-amino-8-azabicyclo[3.2.1]oct-8-yl)pyridin-3-yl]-3-(1-methylpiperidin-4-yl)propan-1-one hydrochloride salt (51 mg, 0.13 mmol) in N,N-dimethylformamide (0.5 mL) was added and stirring was continued for 18 hours. The reaction mixture was diluted with methanol (1.5 mL), and purified by preparatory reverse phase HPLC (ammonium acetate buffered aqueous acetonitrile eluent) to give 2-[(cyclopropylmethyl)amino]-N4-(8-{5-[3-(1-methylpiperidin-4-yl)propanoyl]pyridin-2-yl}-8-azabicyclo[3.2.1]oct-3-endo-yl)benzene-1,4-dicarboxamide as the acetate salt, (54 mg, 66% yield). 1H NMR (400 MHz, d4-Methanol): 8.65 (d, 1H), 7.97 (dd, 1H), 7.54 (d, 1H), 6.96 (d, 1H), 6.82 (dd, 1H), 6.67 (d, 1H), 4.57, (Br, 2H), 3.89 (tr, 1H), 3.04 (m, 2H), 2.95 (d, 2H), 2.87 (tr, 2H), 2.44 (s, 3H), 2.37 (tr, 2H), 2.21-2.01 (m, 6H), 1.91 (br, 1H), 1.88 (br, 1H), 1.80 (s, 3H), 1.78 (m, 1H), 1.58 (q, 4H), 1.38 (br, 1H), 1.22 (m, 2H), 1.02 (m, 1H), 0.47 (m, 2H), 0.20 (m, 2H); MS (EI) for C33H44N6O3: 573 (MH+).

Workup

  1. stirringstirring
  2. waitwas continued for 18 hours
  3. custompurified by preparatory reverse phase HPLC (ammonium acetate buffered aqueous acetonitrile eluent)

Sources & evidence

ORD record
ord-13648988ee454eaaab2c88e6ddc39a53
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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