Piperazine → HCID 10138123, compound

HRID 1057368Notes

Reaction equation

Br[C:2]1[C:3]([O:23][CH3:24])=[CH:4][C:5]2[N:11]([CH2:12][CH3:13])[C:10](=[O:14])[CH:9]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:8][CH2:7][C:6]=2[CH:22]=1.[NH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.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(C)([O-])C.[Na+]>CC([O-])=O.CC([O-])=O.[Pd+2]>[C:18]([O:17][C:15]([CH:9]1[CH2:8][CH2:7][C:6]2[CH:22]=[C:2]([N:25]3[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]3)[C:3]([O:23][CH3:24])=[CH:4][C:5]=2[N:11]([CH2:12][CH3:13])[C:10]1=[O:14])=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

Conditions

Temperature: 80 °C

Procedure

An oven-dried flask, charged with 7-bromo-3(R,S)-tert-butoxycarbonyl-1-ethyl-8-methoxy-2,3,4,5-tetrahydro-1H-1-benzazepine-2-one (48 mg, 0.121 mmol), piperazine (12.64 mg, 0.145 mmol), Pd(OAc)2 (2.72 mg, 0.0121 mmol, 10 mole), BINAP (11.65 mg, 0.0182 mmol) was purged with argon for 5 min. After addition of anhydrous toluene (1 mL) through a syringe followed by sodium tert-butoxide (16.78 mg, 0.169 mmol) in one portion, the flask was purged with argon, vigorously stirred and heated at 80° C. for 22 hrs. The course of the reaction was monitored by TLC. The reaction mixture was diluted with DCM (20 mL), percolated through a short column of Celite and evaporated to dryness. Purification of a crude product using preparative silica TLC developed with MeOH/DCM (1:4) provided the desired compound (8.0 mg, 16%) as a white crystalline product.

Workup

customwas purged with argon for 5 min
additionAfter addition of anhydrous toluene (1 mL) through a syringe
customthe flask was purged with argon
additionThe reaction mixture was diluted with DCM (20 mL)
customevaporated to dryness
customPurification of a crude product

Sources & evidence

ORD record: ord-c601ca89a0ac4971ae190dd38f2d9838
Source dataset: uspto-grants-2003_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06514965B1

Reaction notes

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