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 2385241Notes

Reaction equation

HRID 2385241 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].N1C2C(=CC=CC=2)[C:27]2([CH2:37][O:36][C:35]3[CH:38]=C4C(=C[C:34]2=3)CCO4)C1=O.CC1C=CC(S(OC[C@H]2CCCO2)(=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]([CH2:38][C@H:35]5[CH2:34][CH2:27][CH2:37][O:36]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

5

Reactant 4

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)-dioneHCID 592633545,6-dihydro-2H-spiro[benzofuro[6,5-b]furan-3,3'-indolin]-2'-one

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 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-407fbbf54acb4d53a9fd528c6feadffb
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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