Ethanolamine → [2-(2-Hydroxy-ethylcarbamoyl)-6-oxo-5,6-dihydro-1H-[1,2]diazepino[4,5,6-cd]indol-8-yl]-carbamic acid tert-butyl ester

HRID 2375099Notes

Reaction equation

HRID 2375099 reaction equation
[NH2:1][CH2:2][CH2:3][OH:4].CO.CO[C:9]([C:11]1[NH:12][C:13]2[CH:14]=[C:15]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:16]=[C:17]3[C:23](=[O:24])[NH:22][N:21]=[CH:20][C:19]=1[C:18]=23)=[O:10].C(N(CC)CC)C>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:29]([O:28][C:26](=[O:27])[NH:25][C:15]1[CH:16]=[C:17]2[C:23](=[O:24])[NH:22][N:21]=[CH:20][C:19]3=[C:11]([C:9](=[O:10])[NH:1][CH2:2][CH2:3][OH:4])[NH:12][C:13]([CH:14]=1)=[C:18]23)([CH3:32])([CH3:31])[CH3:30]

Participants

7

Reactant 4

HCID 700Ethanolamine2×HCID 887MethanolHCID 8471TriethylamineHCID 1361816128-tert-Butoxycarbonylamino-6-oxo-5,6-dihydro-1H-[1,2]diazepino[4,5,6-cd]indole-2-carboxylic acid methyl ester

Product 1

HCID 136181667[2-(2-Hydroxy-ethylcarbamoyl)-6-oxo-5,6-dihydro-1H-[1,2]diazepino[4,5,6-cd]indol-8-yl]-carbamic acid tert-butyl esterYield 39%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

Preparation of example 162 was carried out in a manner analogous to step 5 of Example 147, except that 2-aminoethanol was substituted for methanol, and chromatography was not required. Thus CO was bubbled through a mixture of Intermediate 147(d) from Example 147 (60 mg, 0.16 mmol), triethylamine (0.044 mL, 0.32 mmol), 2-aminoethanol (19 mg, 0.32 mmol), and 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) (26 mg, 0.032 mmol) in N,N-dimethylformamide (3.0 mL). After the reaction was complete, the mixture was filtered through diatomaceous earth. The filtrate was concentrated, and methanol was added. The resulting solids were collected by filtration and washed with methanol, dichloromethane and diethyl ether. After drying under vacuum, the title compound (24 mg, 0.062 mmol) was obtained as a yellow powder in 39% yield.

Workup

  1. customPreparation of example 162
  2. filtrationthe mixture was filtered through diatomaceous earth
  3. concentrationThe filtrate was concentrated
  4. additionmethanol was added
  5. filtrationThe resulting solids were collected by filtration
  6. washwashed with methanol, dichloromethane and diethyl ether
  7. customAfter drying under vacuum

Sources & evidence

ORD record
ord-6ec24aee998543ea86c770f1c17ff5b0
Source dataset
uspto-grants-2008_12
Patent number
US07462713B2

Reaction notes

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