6-[5-(9,9-Difluoro-7-{2-[2-(2-methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-benzoimidazol-5-yl}-9H-fluoren-2-yl)-1H-pyrrol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester → HCID 66621511, compound

HRID 72027Notes

Reaction equation

HRID 72027 reaction equation
C(OC([N:11]1[CH:17]([C:18]2[NH:19][C:20]([C:23]3[CH:35]=[CH:34][C:33]4[C:32]5[C:27](=[CH:28][C:29]([C:36]6[CH:62]=[CH:61][C:39]7[N:40]=[C:41]([CH:43]8[CH:48]9[CH2:49][CH:45]([CH2:46][CH2:47]9)[N:44]8[C:50](=[O:60])[CH:51]([NH:55][C:56]([O:58][CH3:59])=[O:57])[CH:52]([CH3:54])[CH3:53])[NH:42][C:38]=7[CH:37]=6)=[CH:30][CH:31]=5)[C:26]([F:64])([F:63])[C:25]=4[CH:24]=3)=[CH:21][CH:22]=2)[CH2:16][C:13]2([CH2:15][CH2:14]2)[CH2:12]1)=O)C1C=CC=CC=1>[Pd].C(O)C>[CH3:59][O:58][C:56](=[O:57])[NH:55][CH:51]([C:50]([N:44]1[CH:43]([C:41]2[NH:42][C:38]3[CH:37]=[C:36]([C:29]4[CH:30]=[CH:31][C:32]5[C:33]6[C:25](=[CH:24][C:23]([C:20]7[NH:19][C:18]([CH:17]8[CH2:16][C:13]9([CH2:14][CH2:15]9)[CH2:12][NH:11]8)=[CH:22][CH:21]=7)=[CH:35][CH:34]=6)[C:26]([F:64])([F:63])[C:27]=5[CH:28]=4)[CH:62]=[CH:61][C:39]=3[N:40]=2)[CH:48]2[CH2:49][CH:45]1[CH2:46][CH2:47]2)=[O:60])[CH:52]([CH3:54])[CH3:53]

Participants

4

Reactant 1

HCID 666205556-[5-(9,9-Difluoro-7-{2-[2-(2-methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-benzoimidazol-5-yl}-9H-fluoren-2-yl)-1H-pyrrol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester

Product 1

HCID 66621511HCID 66621511, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolvent

Procedure

A mixture of 6-[5-(9,9-Difluoro-7-{2-[2-(2-methoxycarbonylamino-3-methyl-butyryl)-2-aza-bicyclo[2.2.1]hept-3-yl]-3H-benzoimidazol-5-yl}-9H-fluoren-2-yl)-1H-pyrrol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid benzyl ester (127 mg) and 10% palladium on carbon, wet (29 mg) in ethanol (4 mL) was stirred under an hydrogen atmosphere for 18 h. Added more and 10% palladium on carbon, wet (50 mg) and continued reaction for 30 h. Reaction mixture was filtered through a pad of CELITE, concentrated and purified by flash column chromatography (silica gel, 5 to 20% methanol/dichloromethane) to give {1-[3-(6-{7-[5-(5-Aza-spiro[2.4]hept-6-yl)-1H-pyrrol-2-yl]-9,9-difluoro-9H-fluoren-2-yl}-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carbonyl]-2-methyl-propyl}-carbamic acid methyl ester as a pale yellow film (21 mg).

Workup

  1. additionAdded more
  2. customreaction for 30 h
  3. customReaction mixture
  4. filtrationwas filtered through a pad of CELITE
  5. concentrationconcentrated
  6. custompurified by flash column chromatography (silica gel, 5 to 20% methanol/dichloromethane)

Sources & evidence

ORD record
ord-e71d38f2100e49e5845d358ff3f975a3
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Reaction notes

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