Acetic Acid → HCID 86669674, compound

HRID 1623929Notes

Reaction equation

HRID 1623929 reaction equation
O=[C:2]1[CH2:6][CH2:5][CH2:4][C:3]1([NH:8][C:9]([C:11]1[C:12]2[CH2:13][C@H:14]3[CH2:27][C@H:15]3[C:16]=2[N:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])[N:18]=1)=[O:10])[CH3:7].[CH3:28][NH:29][CH3:30].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.C(O)(=O)C.C1COCC1>[CH3:28][N:29]([CH2:7][C:3]1([NH:8][C:9]([C:11]2[C:12]3[CH2:13][C@H:14]4[CH2:27][C@H:15]4[C:16]=3[N:17]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=3[F:26])[N:18]=2)=[O:10])[CH2:2][CH2:6][CH2:5][CH2:4]1)[CH3:30]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 674Dimethylamine2×HCID 5049666Sodium triacetoxyborohydride2×HCID 86669672HCID 86669672, compound

Product 1

HCID 86669674HCID 86669674, compoundYield 20.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of (1aR,5aR)-2-(2,4-difluoro-phenyl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid (1-oxo-methyl-cyclopentyl)-amide (26 mg, 0.070 mmol) in methanol (0.5 mL) was added a 2.0 M THF solution of dimethylamine (0.088 mL, 0.175 mmol) and acetic acid (0.681 μL, 0.012 mmol). The mixture was stirred at 23° C. for 15 min, added sodium triacetoxyborohydride (16.3 mg, 0.077 mmol), and stirred for another 1.5 h. One drop of acetic acid was added and the stirring was continued at room temperature for 3 h. Additional sodium triacetoxyborohydride (20 mg) and 2 M dimethylamine (200 μL) was added and the stirring was continued for 3 days. The mixture was purified by preparative TLC to provide the title compound (5.7 mg) as a colorless solid. LCMS m/z=401.5 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 0.48 (td, J=4.8, 3.3 Hz, 1H), 1.13 (td, J=7.8, 4.9 Hz, 1H), 1.58-1.68 (m, 2H), 1.76-1.83 (m, 4H), 2.09-2.18 (m, 3H), 2.22-2.28 (m, 1H), 2.39 (s, 6H), 2.76-2.85 (m, 2H), 2.94 (d, J=16.4 Hz, 1H), 3.04 (dd, J=16.4, 6.3 Hz, 1H), 6.97-7.04 (m, 2H), 7.12 (s, 1H), 7.62-7.68 (m, 1H).

Workup

  1. stirringstirred for another 1.5 h
  2. waitthe stirring was continued at room temperature for 3 h
  3. waitthe stirring was continued for 3 days
  4. customThe mixture was purified by preparative TLC

Sources & evidence

ORD record
ord-a7314180005c4a33afee6a4af941c645
Source dataset
uspto-grants-2014_07
Patent number
US08778950B2

Reaction notes

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