Tris(hydroxymethyl)aminomethane → HCID 86612294, compound

HRID 2074427Notes

Reaction equation

HRID 2074427 reaction equation
C1(N)C(F)=C(F)C(F)=C(N)C=1F.Cl.Cl.[OH-].[Na+].[NH2:17][CH2:18][CH2:19][N:20]1[CH2:25][CH2:24][CH:23]([C@@H:26]2[CH2:35][C:34]3[C:29](=[CH:30][CH:31]=[C:32]([CH3:38])[C:33]=3[O:36][CH3:37])[C@H:28]([CH2:39][NH:40][CH:41]=[O:42])[O:27]2)[CH2:22][CH2:21]1.[F:43][C:44]1[CH:52]=[CH:51][C:47]([C:48](Cl)=[O:49])=[CH:46][CH:45]=1.C(O)C(N)(CO)CO>C(Cl)(Cl)Cl.ClCCl>[F:43][C:44]1[CH:52]=[CH:51][C:47]([C:48]([NH:17][CH2:18][CH2:19][N:20]2[CH2:25][CH2:24][CH:23]([C@@H:26]3[CH2:35][C:34]4[C:29](=[CH:30][CH:31]=[C:32]([CH3:38])[C:33]=4[O:36][CH3:37])[C@H:28]([CH2:39][NH:40][CH:41]=[O:42])[O:27]3)[CH2:22][CH2:21]2)=[O:49])=[CH:46][CH:45]=1

Participants

8

Reactant 5

HCID 6503Tris(hydroxymethyl)aminomethaneHCID 14798Sodium HydroxideHCID 678794-Fluorobenzoyl chloride2×HCID 149026Tetrafluoro-m-phenylenediamine dihydrochlorideHCID 86612295HCID 86612295, compound

Product 1

HCID 86612294HCID 86612294, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 6344DichloromethaneSolvent

Procedure

(1R,3S)-N-{3-[1-(2-Amino-ethyl)-piperidin-4-yl]-5-methoxy-6-methyl-isochroman-1-ylmethyl}formamide was obtained by distributing the dihydrochloride between aqueous sodium hydroxide and dichloromethane and then evaporating the organic phase. To a mixture of IRA-67 (1.2 g) and (1R,3S)-N-{3-[1-(2-amino-ethyl)-piperidin-4-yl]-5-methoxy-6-methyl-isochroman-1-ylmethyl}formamide (0.3 g, 0.69 mmole) add chloroform (12 mL) and 4-fluorobenzoyl chloride (0.310 g, 1.95 mmole) in chloroform (2 mL). After 24 hours add additional 4-fluorobenzoyl chloride (0.3 g, 1.89 mmole) and IRA-67 (2 g). After an additional 18 hours add PS-trisamine (1.0 g of 3.75 mmole/g) and stir for 6 hours. Filter and concentrate, then flush the product over a 35 g silica gel cartridge (eluting with ammonium hydroxide:methanol:ethyl acetate 1:4:95). Collect the appropriate fraction and concentrate to obtain the title compound. CIMS 484, tR (min)=0.46.

Workup

  1. customevaporating the organic phase
  2. filtrationFilter
  3. concentrationconcentrate
  4. customflush the product
  5. washover a 35 g silica gel cartridge (eluting with ammonium hydroxide:methanol:ethyl acetate 1:4:95)
  6. customCollect the appropriate fraction
  7. concentrationconcentrate

Sources & evidence

ORD record
ord-c2e52fbbcaf341fdbfc4f5b5193c0906
Source dataset
uspto-grants-2011_04
Patent number
US07919508B2

Reaction notes

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