Methanol → N-Cyclopropyl-3-(2-(cyclopropylmethyl)-4-((4-(2-hydroxyethyl)-1,4-diazepan-1-yl)methyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-5-fluoro-4-methylbenzamide

HRID 907309Notes

Reaction equation

HRID 907309 reaction equation
[N:1]1([CH2:8][CH2:9][OH:10])[CH2:7][CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH:11]1([NH:14][C:15](=[O:41])[C:16]2[CH:21]=[C:20]([F:22])[C:19]([CH3:23])=[C:18]([C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][CH:33]=3)[C:30](=[O:34])[N:29]([CH2:35][CH:36]3[CH2:38][CH2:37]3)[CH:28]=[C:27]4[CH:39]=O)[CH:17]=2)[CH2:13][CH2:12]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO>ClCCl>[CH:11]1([NH:14][C:15](=[O:41])[C:16]2[CH:21]=[C:20]([F:22])[C:19]([CH3:23])=[C:18]([C:24]3[CH:25]=[C:26]4[C:31](=[CH:32][CH:33]=3)[C:30](=[O:34])[N:29]([CH2:35][CH:36]3[CH2:37][CH2:38]3)[CH:28]=[C:27]4[CH2:39][N:4]3[CH2:5][CH2:6][CH2:7][N:1]([CH2:8][CH2:9][OH:10])[CH2:2][CH2:3]3)[CH:17]=2)[CH2:12][CH2:13]1

Participants

6

Reactant 4

HCID 887MethanolHCID 27365502-(1,4-Diazepan-1-yl)ethan-1-olHCID 5049666Sodium triacetoxyborohydrideHCID 57551841N-Cyclopropyl-3-(2-(cyclopropylmethyl)-4-formyl-1-oxo-1,2-dihydroisoquinolin-6-yl)-5-fluoro-4-methylbenzamide

Product 1

HCID 57551781N-Cyclopropyl-3-(2-(cyclopropylmethyl)-4-((4-(2-hydroxyethyl)-1,4-diazepan-1-yl)methyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-5-fluoro-4-methylbenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(1,4-Diazepan-1-yl)ethanol (311 mg) was added to a suspension of the product of Example 75 step i) (301 mg) in dichloromethane (5 mL). The reaction was stirred at room temperature for 1 hour before the addition of sodium triacetoxyborohydride (457 mg). The reaction was then stirred at room temperature for 1 hour. The reaction mixture was treated with methanol (2 mL) and then concentrated to dryness. The resulting material was purified by HPLC then by SCX ion exchange chromatography (eluting with methanol followed by 1.5M methanolic ammonia). The fractions containing product were concentrated to dryness and the residue triturated with acetonitrile to afford the title compound as a solid (300 mg).

Workup

  1. concentrationconcentrated to dryness
  2. customThe resulting material was purified by HPLC
  3. washby SCX ion exchange chromatography (eluting with methanol followed by 1.5M methanolic ammonia)
  4. additionThe fractions containing product
  5. concentrationwere concentrated to dryness
  6. customthe residue triturated with acetonitrile

Sources & evidence

ORD record
ord-61a1ef688212433f96cb7811de1ad913
Source dataset
uspto-grants-2011_09
Patent number
US08012979B2

Reaction notes

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