Binap, (A+-)- → 4-chloro-6-[3-(2-morpholin-4-yl-ethylamino)-benzylamino]-2H-phthalazin-1-one

HRID 1667498Notes

Reaction equation

Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([NH:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[CH:7]=[CH:8][CH:9]=1.Br[C:20]1[CH:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[C:26](=[O:30])[NH:25][N:24]=[C:23]2[Cl:31].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(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].CC(N(C)C)=O>[Cl:31][C:23]1[C:22]2[C:27](=[CH:28][CH:29]=[C:20]([NH:2][CH2:3][C:4]3[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][CH2:11][CH2:12][N:13]4[CH2:18][CH2:17][O:16][CH2:15][CH2:14]4)[CH:5]=3)[CH:21]=2)[C:26](=[O:30])[NH:25][N:24]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of (3-aminomethyl-phenyl)-(2-morpholin-4-yl-ethyl)-amine hydrochloride (212 mg, 0.781 mmol), 6-bromo-4-chloro-2H-phthalazin-1-one (184 mg, 0.710), Pd2(dba)3 (65 mg, 0.071 mmol), rac-BINAP (142 mg, 0.228 mmol), NaOtBu (266 mg, 2.768 mmol) and DMA (5 mL) was heated to 85° C. until the reaction was completed by HPLC. The reaction was filtered through celite and purified by preparatory HPLC to yield 4-chloro-6-[3-(2-morpholin-4-yl-ethylamino)-benzylamino]-2H-phthalazin-1-one hydroformate (62 mg) as a light brown solid. 1H (400 MHz, d6-DMSO) δ: 2.29 (m, 4H), 2.36 (t, 2H), 3.02 (m, 2H), 3.48 (m, 4H), 4.24 (d, 2H), 5.38 (bs, 1H), 6.40 (dd, 1H), 6.47 (d, 1H), 6.51 (s, 1H), 6.77 (s, 1H), 6.97 (t, 1H), 7.07 (dd, 1H), 7.54 (t, 1H), 7.85 (d, 1H), 8.10 (s, 1H), 12.26 (s, 1H) ppm; m/z (M+1) 413.93.

Workup

filtrationThe reaction was filtered through celite
custompurified by preparatory HPLC

Sources & evidence

ORD record: ord-ca332e95825c42c1a29b72aac56b6644
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044041B2

Reaction notes

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