L-Alaninol → HCID 68294972, compound

HRID 2279591Notes

Reaction equation

Cl[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][N:3]=1.[NH2:19][C@@H:20]([CH3:23])[CH2:21][OH:22].O(C(C)(C)C)[Na]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[OH:22][CH2:21][C@@H:20]([NH:19][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:9]2)=[CH:4][N:3]=1)[CH3:23]

Participants

Conditions

Temperature: 90 °C

Procedure

A vial was charged with tert-butyl 7-chloro-3,4-dihydro-2,6-naphthyridine-2(1H)-carboxylate (175 mg, 0.651 mmol, CASRN 1060816-50-3), Pd2(dba)3 (29.8 mg, 0.0326 mmol), Binap-rac (40.5 mg, 0.0651 mmol), (S)-2-aminopropan-1-ol (97.8 mg, 1.30 mmol), and NaO-tert-Bu (125 mg, 1.30 mmol) and toluene (3 mL), sealed, degassed with nitrogen for 5 min then heated to 90° C. for 4 h. The reaction was cooled and filtered through a plug of CELITE. The filtrate was concentrated and the resulting residue was purified by reverse phase chromatography (SP4) eluting with a MeCN/H2O gradient (5-95% ACN) to afford 56 mg (28%) of (S)-tert-butyl 7-(1-hydroxypropan-2-ylamino)-3,4-dihydro-2,6-naphthyridine-2(1H)-carboxylate (326).

Workup

customsealed
customdegassed with nitrogen for 5 min
temperatureThe reaction was cooled
filtrationfiltered through a plug of CELITE
concentrationThe filtrate was concentrated
customthe resulting residue was purified by reverse phase chromatography (SP4)
washeluting with a MeCN/H2O gradient (5-95% ACN)

Sources & evidence

ORD record: ord-08cc88b28b2549f29f7a1bcc12e8e714
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133187B2

Reaction notes

Loading…