P-Anisidine → HCID 22396548, compound

HRID 2306988Notes

Reaction equation

HRID 2306988 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.CC(C)N=C=NC(C)C.[C:19]([O:23][C:24]([N:26]1[CH2:39][CH2:38][C:37]2[C:36]3[CH:35]=[C:34]([Cl:40])[C:33]([Cl:41])=[CH:32][C:31]=3[N:30]([CH2:42][C:43](O)=[O:44])[C:29]=2[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20]>CN(C1C=CN=CC=1)C.C1COCC1.CCOC(C)=O>[Cl:41][C:33]1[C:34]([Cl:40])=[CH:35][C:36]2[C:37]3[CH2:38][CH2:39][N:26]([C:24]([O:23][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:25])[CH2:27][CH2:28][C:29]=3[N:30]([CH2:42][C:43]([NH:9][C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[O:44])[C:31]=2[CH:32]=1

Participants

7

Reactant 3

HCID 7732P-AnisidineHCID 12734DiisopropylcarbodiimideHCID 22396895HCID 22396895, compound

Product 1

HCID 22396548HCID 22396548, compoundYield 32.6%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

DMAP (60 mg, 0.49 mmol), p-anisidine (66 mg, 0.54 mmol) and DIC (0.084 mL, 0.54 mmol) were added to the solution of crude [3-(tert-butoxycarbonyl)-8,9-dichloro-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl]acetic acid (0.20 g, 0.48 mmol) in dry THF (2.5 mL). After 18 h, the reaction was diluted with EtOAc and washed with 10% aqueous citric acid, saturated aqueous NaHCO3, and brine. The organic layer was then dried over Na2SO4, decanted, and concentrated. The crude product was first purified by column chromatography (Biotage, 40S, SIM) with CH2Cl2/EtOAc (gradient, 99:1 to 95:5) to give 81 mg of impure product. Then, crystallization from EtOAc/heptane gave 73 mg (29%) of a white solid: mp 151-151.5° C.; IR (diffuse reflectance) 3288, 1695, 1661, 1550, 1513, 1473, 1422, 1367, 1318, 1269, 1250, 1172, 1161, 1118, 831 cm−1; MS (CI) m/z 518 (M+H+), 222, 221, 220, 167, 166, 124, 59, 58, 52, 51; Anal. Calcd for C26H29Cl2N3O4: C, 60.24; H, 5.64; N, 8.10; found: C, 60.23; H, 5.73; N, 8.10.

Workup

  1. washwashed with 10% aqueous citric acid, saturated aqueous NaHCO3, and brine
  2. dry with materialThe organic layer was then dried over Na2SO4
  3. customdecanted
  4. concentrationconcentrated
  5. customThe crude product was first purified by column chromatography (Biotage, 40S, SIM) with CH2Cl2/EtOAc (gradient, 99:1 to 95:5)

Sources & evidence

ORD record
ord-9a082d354d2d429eaf1fe8feb13c16d6
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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