2-(Bromomethyl)tetrahydro-2H-pyran → 1-methyl-1'-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3'-indole]-2,2'(1'H,3H)-dione

HRID 1407664Notes

Reaction equation

HRID 1407664 reaction equation
[CH3:1][N:2]1[C:7]2[CH:8]=[C:9]3[C:14]4([C:22]5[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=5)[NH:16][C:15]4=[O:23])[CH2:13][O:12][C:10]3=[CH:11][C:6]=2[O:5][CH2:4][C:3]1=[O:24].CC1C=CC(S(O[CH2:36][C@H:37]2[CH2:41][CH2:40][CH2:39][O:38]2)(=O)=O)=CC=1.BrCC1CCCCO1>>[CH3:1][N:2]1[C:7]2[CH:8]=[C:9]3[C:14]4([C:22]5[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=5)[N:16]([CH2:36][C@H:37]5[CH2:41][CH2:40][CH2:39][O:38]5)[C:15]4=[O:23])[CH2:13][O:12][C:10]3=[CH:11][C:6]=2[O:5][CH2:4][C:3]1=[O:24]

Participants

4

Reactant 3

HCID 1419172-(Bromomethyl)tetrahydro-2H-pyranHCID 7033050(R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonateHCID 461957101-methyl-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3'-indole]-2,2'(1'H,3H)-dione

Product 1

HCID 593521591-methyl-1'-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3'-indole]-2,2'(1'H,3H)-dione

Procedure

Following the procedure as described in EXAMPLE 4 and making non-critical variations using 1-methyl-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3′-indole]-2,2′(1′H,3H)-dione to replace 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2″(1′H)-one, and (R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate to replace 2-(bromomethyl)tetrahydro-2H-pyran, 1-methyl-1′-[(2R)-tetrahydrofuran-2-ylmethyl]-1H-spiro[furo[3,2-g][1,4]benzoxazine-8,3′-indole]-2,2′(1′H,3H)-dione was obtained (69%) as as an off-white solid: mp 79-81° C. (diethyl ether); 1H NMR (300 MHz, CDCl3) δ7.33 (dd, J=7.8, 7.8 Hz, 1H), 7.16-7.04 (m, 3H), 6.63-6.62 (m, 1H), 6.39-6.32 (m, 1H), 4.96-4.92 (m, 1H), 4.72-4.67 (m, 1H), 4.54 (s, 2H), 4.37-4.26 (m, 1H), 3.98-3.85 (m, 2H), 3.82-3.70 (m, 2H), 3.15 (s, 3H), 2.13-2.00 (m, 1H), 1.98-1.88 (m, 2H), 1.78-1.65 (m, 1H); 13C NMR (75 MHz, CDCl3) δ177.7 (2C), 163.9 (2C), 157.4, 157.3, 146.9 (2C), 143.1, 142.6, 132.2, 131.9, 129.2, 129.1, 124.4 (2C), 123.8 (2C), 123.5, 123.1, 122.8, 109.8, 109.7, 109.6, 100.1 (2C), 80.8, 80.6, 76.9, 76.2, 68.4, 68.2, 67.7, 58.1 (2C), 44.9, 44.6, 29.3, 29.1, 28.5, 28.4, 25.7 (2C); MS (ES+) m/z 429.1 (M+23), 407.1 (M+1).

Sources & evidence

ORD record
ord-73b809272f134dd4be7025f88db4eeb4
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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