N,N-Dibutyl-4-chloro-5-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazole-3-carboxamide → Ethyl 4-(4-chloro-3-(dibutylcarbamoyl)-5-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

HRID 528931Notes

Reaction equation

HRID 528931 reaction equation
[CH2:1]([N:5]([CH2:23][CH2:24][CH2:25][CH3:26])[C:6]([C:8]1[C:12]([Cl:13])=[C:11]([CH2:14][CH2:15][O:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[NH:10][N:9]=1)=[O:7])[CH2:2][CH2:3][CH3:4].F[C:28]1[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][C:29]=1[C:39]([N:41]1[CH2:50][CH2:49][C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[CH2:42]1)=[O:40]>>[Cl:13][C:12]1[C:8]([C:6](=[O:7])[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[CH2:23][CH2:24][CH2:25][CH3:26])=[N:9][N:10]([C:28]2[CH:38]=[CH:37][C:31]([C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:30][C:29]=2[C:39]([N:41]2[CH2:50][CH2:49][C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[CH2:42]2)=[O:40])[C:11]=1[CH2:14][CH2:15][O:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][O:18]1

Participants

3

Reactant 2

HCID 71060785N,N-Dibutyl-4-chloro-5-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazole-3-carboxamideHCID 71061015Ethyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

Product 1

HCID 71062312Ethyl 4-(4-chloro-3-(dibutylcarbamoyl)-5-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoateYield 30%

Procedure

Following a procedure analogous to that for the synthesis of Intermediate 1E, N,N-dibutyl-4-chloro-5-(2-(tetrahydro-2H-pyran-2-yloxy)ethyl)-1H-pyrazole-3-carboxamide (407 mg, 1.06 mmol) and ethyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (380 mg, 1.16 mmol) were converted to the title compound (219 mg, 30%). 1H NMR (CD3OD, mixture of amide rotamers) δ 8.26 (td, J=8.4, 1.8 Hz, 1H), 8.19-8.10 (m, 1H), 7.98 (d, J=8.1 Hz, 1H), 7.29-7.07 (m, 3.5H), 6.94 (d, J=7.5 Hz, 0.5H), 4.71-4.48 (m, 2H), 4.47-4.39 (m, 2H), 4.16-3.86 (m, 1H), 3.80-3.37 (m, 5H), 3.26-2.58 (m, 5H), 1.87-0.74 (m, 22H), 0.72-0.66 (m, 1H); MS(ESI+) m/z 609.3 (M+H-THP)+.

Sources & evidence

ORD record
ord-b6548ea74eda4fb89405ce7360e2cd28
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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