Acetic Acid → 4-{4-(4-Fluorophenyl)-1-[1-(pyrimidin-2-ylmethyl)azetidin-3-yl]-1H-imidazol-5-yl}pyrimidin-2-amine

HRID 1896644Notes

Reaction equation

HRID 1896644 reaction equation
[NH:1]1[CH2:4][CH:3]([N:5]2[C:9]([C:10]3[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=3)=[C:8]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[N:7]=[CH:6]2)[CH2:2]1.[N:24]1[CH:29]=[CH:28][CH:27]=[N:26][C:25]=1[CH:30]=O.C(N(CC)CC)C.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[F:23][C:20]1[CH:21]=[CH:22][C:17]([C:8]2[N:7]=[CH:6][N:5]([CH:3]3[CH2:2][N:1]([CH2:30][C:25]4[N:26]=[CH:27][CH:28]=[CH:29][N:24]=4)[CH2:4]3)[C:9]=2[C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH2:16])[N:11]=2)=[CH:18][CH:19]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 13751953Pyrimidine-2-carbaldehydeHCID 574617124-[1-Azetidin-3-yl-4-(4-fluorophenyl)-1H-imidazol-5-yl]pyrimidin-2-amine

Product 1

HCID 582351324-{4-(4-Fluorophenyl)-1-[1-(pyrimidin-2-ylmethyl)azetidin-3-yl]-1H-imidazol-5-yl}pyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 4-[1-azetidin-3-yl-4-(4-fluorophenyl)-1H-imidazol-5-yl]pyrimidin-2-amine (C5) (11.2 mg, 0.0361 mmol), pyrimidine-2-carbaldehyde (5.9 mg, 0.055 mmol), triethylamine (0.010 mL, 0.072 mmol) and acetic acid (0.010 mL, 0.17 mmol) in 1,2-dichloroethane (1.0 mL) was stirred for 30 minutes. Sodium triacetoxyborohydride (22.9 mg, 0.11 mmol) was added and stirring was continued for an additional 18 hours, at which time the reaction was quenched with dilute aqueous sodium hydroxide solution. Extraction of the aqueous layer with 1,2-dichloroethane was followed by combination of the organic layers and concentration in vacuo. Purification of the residue was effected by reversed-phase HPLC (Gradient: 5% to 60% acetonitrile in water) to provide the product as a yellow oil. Yield: 1 mg, 0.0025 mmol, 7%. LCMS m/z 403.6 (M+1). 1H NMR (400 MHz, CD3OD) δ 3.66-3.70 (m, 2H), 3.96-4.00 (m, 2H), 4.02 (s, 2H), 5.34 (m, 1H), 6.38 (d, J=5.2 Hz, 1H), 7.10 (dd, J=8.8, 8.8 Hz, 2H), 7.38 (t, J=4.9 Hz, 1H), 7.44 (dd, J=8.9, 5.4 Hz, 2H), 8.09 (d, J=5.2 Hz, 1H), 8.24 (br s, 1H), 8.77 (d, J=5.0 Hz, 2H).

Workup

  1. stirringstirring
  2. waitwas continued for an additional 18 hours, at which time
  3. customthe reaction was quenched with dilute aqueous sodium hydroxide solution
  4. extractionExtraction of the aqueous layer with 1,2-dichloroethane
  5. concentrationwas followed by combination of the organic layers and concentration in vacuo
  6. customPurification of the residue

Sources & evidence

ORD record
ord-4f9e7160a2b149b79fc1b061c6d3a342
Source dataset
uspto-grants-2013_08
Patent number
US08518944B2

Reaction notes

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