Dichloromethane → 7-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid ((S)-1-cyclobutyl-pyrrolidin-2-ylmethyl)-quinoxalin-2-ylmethyl-amide

HRID 2220722Notes

Reaction equation

HRID 2220722 reaction equation
C(O[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][N:14]([C:26]([C:28]1[CH:38]=[C:37]([O:39][CH3:40])[C:31]2[O:32][C:33]([CH3:36])([CH3:35])[O:34][C:30]=2[CH:29]=1)=[O:27])[CH2:15][C:16]1[CH:25]=[N:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=1)=O)(C)(C)C.ClCCl.[C:44]1(=O)[CH2:47]C[CH2:45]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>FC(F)(F)C(O)=O.ClCCl.C(=O)(O)[O-].[Na+]>[CH:6]1([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[CH2:13][N:14]([CH2:15][C:16]2[CH:25]=[N:24][C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:17]=2)[C:26]([C:28]2[CH:38]=[C:37]([O:39][CH3:40])[C:31]3[O:32][C:33]([CH3:35])([CH3:36])[O:34][C:30]=3[CH:29]=2)=[O:27])[CH2:47][CH2:44][CH2:45]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 58622231HCID 58622231, compound

Product 1

HCID 586222267-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid ((S)-1-cyclobutyl-pyrrolidin-2-ylmethyl)-quinoxalin-2-ylmethyl-amide

Reagents, catalysts & solvents 2

HCID 516892Sodium BicarbonateSolventHCID 21863450Trifluoroacetic acid methylene chlorideSolvent

Procedure

73 mg of (S)-2-{[(7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl)-quinoxalin-2-ylmethyl-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester were dissolved in 3 mL 10% trifluoroacetic acid/dichloromethane and neutralized with aqueous sodium bicarbonate after 2 hours. The crude material was submitted to reductive amination reaction in dichloromethane using 53 mg (0.67 mmol) of cyclobutanone and 0.14 g (0.67 mmol) sodium triacetoxyborohydride. After overnight the reaction was quenched with aqueous sodium bicarbonate and purified using reverse phase HPLC, mobile phase with a gradient 10-70% acetonitrile in 40 min. The residue was dissolved in dichloromethane, washed with aqueous sodium bicarbonate, dried with anhydrous magnesium sulfate and evaporated in vacuum to yield 42 mg pale yellow solid as the free base. LC-MSD, m/z for C29H34N4O4 [M+H]+: 503.6. 1H NMR (400 MHz, CDCl31HCl): δ 1.7 (s, 6 H), 1.7-3.0 (m, 11 H), 3.6-4.2 (m, 8 H), 5.3-5.4 (m, 1 H), 5.8-5.9 (m, 1 H), 6.6 (s, 1 H), 6.8 (s, 1 H), 8.0 (bs, 2 H), 8.3 (bs, 1 H), 8.5-8.6 (m, 1 H), 9.1 (bs, 1 H), 12.0 (bs, 1 H).

Workup

  1. customAfter overnight the reaction was quenched with aqueous sodium bicarbonate
  2. custompurified
  3. customin 40 min
  4. dissolutionThe residue was dissolved in dichloromethane
  5. washwashed with aqueous sodium bicarbonate
  6. dry with materialdried with anhydrous magnesium sulfate
  7. customevaporated in vacuum

Sources & evidence

ORD record
ord-706d772d25384c5db718ca3c0cfb5b13
Source dataset
uspto-grants-2008_08
Patent number
US07417062B2

Reaction notes

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