1,2-Dichloroethane → (+/-)-(E)-3-{1'-methyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3'-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide

HRID 874314Notes

Reaction equation

HRID 874314 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C:4]2([NH:12][C:11](=[O:13])[C:10]3[CH:14]=[C:15](/[CH:18]=[CH:19]/[C:20](O)=[O:21])[CH:16]=[CH:17][C:9]=3[O:8]2)[CH2:3]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:37][O:38][CH:39]1[CH2:44][CH2:43][CH2:42][CH2:41][O:40]1>C(Cl)Cl>[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][C:4]2([NH:12][C:11](=[O:13])[C:10]3[CH:14]=[C:15](/[CH:18]=[CH:19]/[C:20]([NH:37][O:38][CH:39]4[CH2:44][CH2:43][CH2:42][CH2:41][O:40]4)=[O:21])[CH:16]=[CH:17][C:9]=3[O:8]2)[CH2:3]1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 67071585(+/-)-(E)-3-{1'-methyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3'-piperidin]-6-yl}-acrylic acid

Product 1

HCID 86671993(+/-)-(E)-3-{1'-methyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3'-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamideYield 88.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of (±)-(E)-3-{1′-methyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3′-piperidin]-6-yl}-acrylic acid (208 mg, 0.61 mmol) in DCM (7 ml) was treated with TEA (0.14 ml, 1.0 mmol) and then with EDC (196 mg, 1.03 mmol), HOBt (140 mg, 1.03 mmol) and NH2OTHP (97 mg, 0.82 mmol) following the procedure described in Example 30, Step B, giving (±)-(E)-3-{1′-methyl-3,4-dihydro-4-oxo-spiro[2H-(1,3)-benzoxazine-2,3′-piperidin]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide (217 mg) as a light yellow solid.

Sources & evidence

ORD record
ord-ea5d8ee0b70c4b438abd5fdaf52321ad
Source dataset
uspto-grants-2015_03
Patent number
US08980877B2

Reaction notes

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