Formaldehyde → HCID 15983454, compound

HRID 2220488Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[N:15][CH:16]=2)[CH2:11][NH:10][CH2:9]1.[CH2:28]=O.[BH4-].[Na+]>CO>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]3)=[N:15][CH:16]=2)[CH2:11][N:10]([CH3:28])[CH2:9]1

Participants

Conditions

Temperature: 55 °C

Procedure

A solution of 4-(2-fluoro-phenyl)-7-(3-piperidin-1-yl-propoxy)-1,2,3,4-tetrahydro-[2,6]naphthyridine (50.2 mg, 0.136 mmol) in MeOH (5 mL) was treated with paraformaldehyde (62 mg). The mixture was heated at 55° C. for 1 h, cooled to 0° C., and was treated with NaBH4 (66 mg, 1.74 mmol). After 2 h at 0° C., the mixture was diluted with satd. aq. NaHCO3 and extracted with DCM. The organic layer was dried and concentrated. The residue was chromatographed (SiO2; 1-10% 2 M NH3 in MeOH/DCM) to give the title compound (20.4 mg, 39%) as an oil. MS (ESI): mass calcd. for C23H30FN3O, 383.24; m/z found, 384.5 [M+H]+. 1H NMR (CDCl3): 7.69 (s, 1H), 7.23-7.17 (m, 1H), 6.47 (s, 1H), 4.57-4.54 (m, 1H), 4.26 (t, J=6.7, 2H), 3.62 (d, J=15.9, 1H), 3.58 (d, J=15.9, 1H), 2.97 (dd, J=12.0, 5.1, 1H), 2.65 (dd, J=11.5, 7.5, 1H), 2.47-2.36 (m, 9H), 1.98-1.91 (m, 2H), 1.61-1.55 (m, 4H), 1.47-1.39 (m, 2H).

Workup

temperaturecooled to 0° C.
additionthe mixture was diluted with satd
extractionaq. NaHCO3 and extracted with DCM
customThe organic layer was dried
concentrationconcentrated
customThe residue was chromatographed (SiO2; 1-10% 2 M NH3 in MeOH/DCM)

Sources & evidence

ORD record: ord-d4b3ca55cbbb4af8b1ea00fc6573ebb3
Source dataset: uspto-grants-2008_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07417054B2

Reaction notes

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