Diisopropylethylamine → HCID 178488318, compound

HRID 245747Notes

Reaction equation

HRID 245747 reaction equation
[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[C:6]([C:13](Cl)=[O:14])[N:7]2[CH3:12].[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[N:24]=[C:25]([C@H:33]3[CH2:38][CH2:37][C@H:36]([N:39]4[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]4)[CH2:35][CH2:34]3)[N:26]3[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[C:27]=23)=[CH:19][C:18]=1[OH:46].C(N(CC)C(C)C)(C)C>ClCCl>[OH:46][C:18]1[CH:19]=[C:20]([C:23]2[N:24]=[C:25]([C@H:33]3[CH2:38][CH2:37][C@H:36]([N:39]4[CH2:44][CH2:43][N:42]([CH3:45])[CH2:41][CH2:40]4)[CH2:35][CH2:34]3)[N:26]3[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[C:27]=23)[CH:21]=[CH:22][C:17]=1[NH:16][C:13]([C:6]1[N:7]([CH3:12])[C:8]2[C:4]([CH:5]=1)=[C:3]([O:2][CH3:1])[CH:11]=[CH:10][CH:9]=2)=[O:14]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 866746604-methoxy-1-methyl-1H-indole-2-carbonyl chlorideHCID 178432916HCID 178432916, compound

Product 1

HCID 178488318HCID 178488318, compoundYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Under a nitrogen atmosphere 4-methoxy-1-methyl-1H-indole-2-carbonyl chloride (described in example 2g) (0.048 mmol, 10.64 mg) was added to a solution of 2-amino-5-(8-methyl-3-((trans)-4-(4-methylpiperazin-1-yl)cyclohexyl)imidazo[1,5-a]pyrazin-1-yl)phenol (116 mg impure material) and N,N-diisopropylethylamine (0.145 mmol, 24 μl) in dichloromethane at 0° C. The mixture was stirred at room temperature for one hour. Purification by column chromatography (silica gel; gradient of dichloromethane to dichloromethane/methanol 5/1) followed by purification with HPLC (column: X-bridge; eluens acetonitrile/methanol/water with constant 0.003M trifluoroacetic acid). Proper fractions were collected and basified with aqueous sodium carbonate, extracted with dichloromethane, organic layer dried (Na2SO4) and concentrated in vacuo to give N-(2-hydroxy-4-(8-methyl-3-((trans)-4-(4-methylpiperazin-1-yl)cyclohexyl)imidazo[1,5-a]pyrazin-1-yl)phenyl)-4-methoxy-1-methyl-1H-indole-2-carboxamide (7 mg)

Workup

  1. customPurification by column chromatography (silica gel; gradient of dichloromethane to dichloromethane/methanol 5/1)
  2. customfollowed by purification with HPLC (column: X-bridge; eluens acetonitrile/methanol/water with constant 0.003M trifluoroacetic acid)
  3. customProper fractions were collected
  4. extractionextracted with dichloromethane, organic layer
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6e2bca722296465e90c482e76f7b9abe
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Reaction notes

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