Acetic Acid → HCID 178424625, compound

HRID 541441Notes

Reaction equation

HRID 541441 reaction equation
[CH3:1][C:2]1[CH:23]=[C:22]([CH3:24])[C:21]([C:25]2[NH:33][C:28]3[CH2:29][NH:30][CH2:31][CH2:32][C:27]=3[N:26]=2)=[CH:20][C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][CH:9]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)=[O:5].[O:34]1[CH2:37][C:36](=O)[CH2:35]1.[B-]C#N.[Na+].C(O)(=O)C>CO.C1COCC1.ClCCl>[CH3:1][C:2]1[CH:23]=[C:22]([CH3:24])[C:21]([C:25]2[NH:26][C:27]3[CH2:32][CH2:31][N:30]([CH:36]4[CH2:37][O:34][CH2:35]4)[CH2:29][C:28]=3[N:33]=2)=[CH:20][C:3]=1[C:4]([N:6]1[CH2:7][CH2:8][CH:9]([C:12]2[CH:13]=[CH:14][C:15]([C:16]#[N:17])=[CH:18][CH:19]=2)[CH2:10][CH2:11]1)=[O:5]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 150242543-OxetanoneHCID 20587905Sodium cyanoborohydride [MI]HCID 68288226HCID 68288226, compound2×

Product 1

HCID 178424625HCID 178424625, compoundYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A mixture of 4-(1-(2,4-dimethyl-5-(4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-2-yl)benzoyl)piperidin-4-yl)benzonitrile (compound 2.9, 62 mg), oxetan-3-one (18 μl), sodium cyanotrihydroborate (18 mg), and acetic acid (80 μl) in MeOH/THF (1:1 v/v) was stirred for 16 hours. The reaction was then diluted with dichloromethane, washed with saturated sodium bicarbonate solution followed by brine. The organic layer was dried (MgSO4) and concentrated. The residue was purified by preparative TLC at 8% MeOH in DCM to give 42 mg white solid (60%). m/z (ES+) 496 (M+H)+. 1H NMR (400 MHz, Chloroform-d) δ 7.63 (d, 2H), 7.32 (d, 2H), 7.27 and 7.20 (2 singlet, amide rotamers, 1H), 7.02 (s, 1H), 4.96 (s, 1H), 4.74 (m, 4H), 3.88-3.77 (m, 1H), 3.63 (d, 1H), 3.49 (d, 2H), 3.08 (t, 1H), 2.97-2.62 (m, 6H), 2.45 (d, 3H), 2.31 and 2.22 (2 singlets, amide rotamers, 3H), 2.11-1.40 (m, 4H).

Workup

  1. washwashed with saturated sodium bicarbonate solution
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated
  4. customThe residue was purified by preparative TLC at 8% MeOH in DCM

Sources & evidence

ORD record
ord-b27a8ccc96174920ae62406c48a41459
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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