Sodium cyanoborohydride → tert-Butyl (2R,5S)-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]-5-{[(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)methyl]amino}piperidine-1-carboxylate

HRID 255348Notes

Reaction equation

[NH2:1][C@@H:2]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@@H:5]([CH2:15][CH2:16][N:17]2[C:22]3[CH:23]=[C:24]([C:27]#[N:28])[CH:25]=[CH:26][C:21]=3[O:20][CH2:19][C:18]2=[O:29])[CH2:4][CH2:3]1.O=[C:31]1[CH2:36][O:35][C:34]2[CH:37]=[CH:38][C:39]([CH:41]=O)=[N:40][C:33]=2[NH:32]1.[BH3-]C#N.[Na+]>CO>[C:27]([C:24]1[CH:25]=[CH:26][C:21]2[O:20][CH2:19][C:18](=[O:29])[N:17]([CH2:16][CH2:15][C@H:5]3[CH2:4][CH2:3][C@H:2]([NH:1][CH2:41][C:39]4[CH:38]=[CH:37][C:34]5[O:35][CH2:36][CH2:31][NH:32][C:33]=5[N:40]=4)[CH2:7][N:6]3[C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[C:22]=2[CH:23]=1)#[N:28]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of tert-butyl (2R,5S)-5-amino-2-[2-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)ethyl]piperidine-1-carboxylate (Intermediate 183, 0.14 g), 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde (WO 2004/058144) (75 mg) and 3 Å molecular sieves powder (70 mg) in methanol (8 mL) was heated at 80° C. for 1 hour. The solution was cooled to 0° C. and NaCNBH3 (33 mg) was added. After stirring at room temperature overnight, the reaction was filtered and concentrated. The residue was purified chromatography on silica gel with a gradient of 0-5% methanol in methylene chloride to give 0.14 g.

Workup

temperatureThe solution was cooled to 0° C.
filtrationthe reaction was filtered
concentrationconcentrated
customThe residue was purified chromatography on silica gel with a gradient of 0-5% methanol in methylene chloride
customto give 0.14 g

Sources & evidence

ORD record: ord-230f11807bf34779986b22046b762dc5
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07875715B2

Reaction notes

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