Cyclopropane → HCID 11591389, compound

HRID 2101193Notes

Reaction equation

HRID 2101193 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([O:14][CH2:15][CH:16]([N:20]2[CH2:29][CH2:28][C:27]3[C:22](=[CH:23][C:24]([O:30][C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=4[F:38])=[CH:25][CH:26]=3)[C:21]2=[O:39])[CH:17]([CH3:19])[CH3:18])[CH2:10][CH2:9]1)=O)(C)(C)C.[C:40](O)([C:42](F)(F)F)=O.[CH2:47]1C[CH2:48]1.CCN(C(C)C)C(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C>ClCCl>[CH:40]1([CH2:42][CH:15]([O:14][CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)[CH:16]([N:20]2[CH2:29][CH2:28][C:27]3[C:22](=[CH:23][C:24]([O:30][C:31]4[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=4[F:38])=[CH:25][CH:26]=3)[C:21]2=[O:39])[CH:17]([CH3:18])[CH3:19])[CH2:48][CH2:47]1

Participants

7

Reactant 5

HCID 6351CyclopropaneHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2724942TriacetoxyborohydrideHCID 57797482HCID 57797482, compound

Product 1

HCID 11591389HCID 11591389, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To the solution of 4-{2-[7-(2,4-difluoro-phenoxy)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-3-methyl-butoxy}-piperidine-1-carboxylic acid tert-butyl ester 15 (40 mg, 0.07 mmol) in dichloromethane (5 mL) was added 1 mL of TFA and the reaction was stirred at room temperature for 2 hours, at which time the solvent was removed and the crude material was re-suspended in dichloroethane, then carboxaldehyde cyclopropane (7.7 mg, 0.11 mmol), DIEA (39 mL, 0.22 mmol), and triacetoxyborohydride (31 mg, 0.148 mmol) were added. The mixture was stirred at 60° C. for six hours, then diluted with 10 mL of CH2Cl2 and extracted with saturated brine (10 mL). The solvent was removed and the crude oil was loaded onto a silica gel column and eluted with 10% MeOH in CH2Cl2 to yield 4.4 mg of 2-[1-(1-cyclopropylmethyl-piperidin-4-yloxymethyl)-2-methyl-propyl]-7-(2,4-difluoro-phenoxy)-3,4-dihydro-2H-isoquinolin-1-one 16 as a white solid. 1H NMR (CDCl3) δ 0.08 (m, 2H), 0.2 (m, 2H), 0.85 (m, 1H), 0.91 (d, J=6.6 Hz, 3H), 1.01 (d, J=6.6 Hz, 3H), 1.62 (m, 2.5H), 1.70 (m, 1H), 1.87 (m, 2.5H), 2.10 (m, 1H), 2.25 (m 3H), 2.78 (m, 2H), 2.89 (m, 2H), 3.30 (n, 1H), 3.49 (m, 1H), 3.59 (m, 1H), 6.84 (m, 1H), 6.90 (m, 1H), 7.06 (m, 2H), 7.14 (d, J=8.3 Hz, 1H), 7.57 (d, J=2.6 Hz, 1H). ESI [M+1] found 499.3; C29H36F2N2O3 requires 498.27.

Workup

  1. customwas removed
  2. stirringThe mixture was stirred at 60° C. for six hours
  3. extractionextracted with saturated brine (10 mL)
  4. customThe solvent was removed
  5. washeluted with 10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-dac37a8fb3d2473285761afb971e8bf9
Source dataset
uspto-grants-2009_08
Patent number
US07572783B2

Reaction notes

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