2-Methylquinoline-6-carboxylic acid → HCID 76902118, compound

HRID 880334Notes

Reaction equation

HRID 880334 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:12]([OH:14])=O)[CH:8]=2)[N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:39][CH2:40][CH:41]([OH:53])[CH2:42][N:43]1[CH2:52][CH2:51][C:50]2[C:45](=[CH:46][CH:47]=[CH:48][CH:49]=2)[CH2:44]1>C(Cl)Cl>[CH2:44]1[C:45]2[C:50](=[CH:49][CH:48]=[CH:47][CH:46]=2)[CH2:51][CH2:52][N:43]1[CH2:42][CH:41]([OH:53])[CH2:40][NH:39][C:12]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([CH3:1])[CH:11]=[CH:10]2)=[O:14]

Participants

5

Reactant 3

HCID 6044832-Methylquinoline-6-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 167907201-amino-3-(3,4-dihydroisoquinolin-2(1H)-yl)propan-2-ol

Product 1

HCID 76902118HCID 76902118, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
15 °C

Procedure

To a solution of 2-methylquinoline-6-carboxylic acid (100 mg, 0.535 mmol) in DCM (20 mL) was added HATU (244 mg, 0.642 mmol) and TEA (162 mg, 1.604 mmol). The mixture was stirred at 15° C. for 30 minutes before 1-amino-3-(3,4-dihydro isoquinolin-2(1H)-yl)propan-2-ol (110 mg, 0.535 mmol) was added. The resulting mixture was stirred for another 16 h at 15° C., at which point LCMS showed the completion of the reaction. The mixture was concentrated and the residue was purified by Preparation HPLC to give the desired title compound (106.2 mg, 53%). 1H NMR (400 MHz, METHANOL-d4) δ=8.32 (d, J=1.9 Hz, 1H), 8.14 (d, J=8.4 Hz, 1H), 8.09 (dd, J=2.1, 8.8 Hz, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.49 (d, J=8.4 Hz, 1H), 7.16-7.08 (m, 3H), 7.08-7.03 (m, 1H), 4.18 (quin, J=6.1 Hz, 1H), 3.79 (s, 2H), 3.59 (d, J=5.8 Hz, 2H), 2.94-2.88 (m, 4H), 2.79-2.68 (m, 5H). LCMS (m/z): 376.0 (M+1).

Workup

  1. additionwas added
  2. customthe completion of the reaction
  3. concentrationThe mixture was concentrated
  4. customthe residue was purified by Preparation HPLC

Sources & evidence

ORD record
ord-96bf742aea974342952ece9d07d31567
Source dataset
uspto-grants-2015_03
Patent number
US08993555B2

Reaction notes

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