Oxalyl chloride → HCID 25171033, compound

HRID 2093592Notes

Reaction equation

HRID 2093592 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:21]([CH3:23])[CH3:22])[C:6]2[O:10][C:9]([C:11]3[CH:19]=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:20]=1)#[N:2].C(Cl)(=O)C(Cl)=O.[NH2:30][CH2:31][CH:32]1[CH2:37][CH2:36][N:35]([C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[O:39])[CH2:34][CH2:33]1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([CH:21]([CH3:23])[CH3:22])[C:6]2[O:10][C:9]([C:11]3[CH:19]=[CH:18][C:14]([C:15]([NH:30][CH2:31][CH:32]4[CH2:37][CH2:36][N:35]([C:38]([O:40][CH2:41][C:42]5[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=5)=[O:39])[CH2:34][CH2:33]4)=[O:16])=[CH:13][CH:12]=3)=[N:8][C:7]=2[CH:20]=1)#[N:2]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 219554994-Aminomethyl-1-N-Cbz-piperidineHCID 573699454-(5-Cyano-7-isopropylbenzo[d]oxazol-2-yl)benzoic acid2×

Product 1

HCID 25171033HCID 25171033, compoundYield 72.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

To a suspension of 4-(5-cyano-7-isopropyl-1,3-benzoxazol-2-yl)benzoic acid (2 g, 6.53 mmol, INTERMEDIATE 2) in dichloromethane (25 ml) were added oxalyl chloride (9.79 ml, 19.59 mmol) and a drop (ca. 10 μl) of dimethylformamide. The mixture was stirred for 1 h at 25° C., at which point a clear solution formed. The mixture was concentrated and then co-concentrated with 5 ml of toluene. To a solution of the residue in dichloromethane (25 ml) was added 4-aminomethyl-1-N-Cbz-piperidine (2 g, 8.05 mmol) and diisopropylethylamine (1.711 ml, 9.79 mmol). The mixture was stirred overnight at 25° C. and then concentrated. The residue was purified by flash chromatography on a Biotage Horizon, 65i column, eluting with 1 column volume of 10% ethyl acetate in hexanes followed by a gradient of 10 to 100% ethyl acetate in hexanes over 10 column volumes to provide the title compound (2.53 g, 72.2%). Mass spectrum (ESI) 537.0 (M+1). 1H NMR (500 MHz, CDCl3): δ 8.29 (m, 2H), 7.94 (d, J=8.5 Hz 2H), 7.90 (m, 1H), 7.49 (s, 1H), 7.27-7.35 (m, 4H), 6.69 (m, 1H), 5.11 (s, 2H), 4.09-4.30 (m, 2H), 3.31-3.49 (m, 3H), 2.79 (m, 2H), 1.86 (m, 1H), 1.77 (m, 2H), 1.45 (d, J=6.5 Hz, 6H), 1.18-1.30 (m, 2H).

Workup

  1. customformed
  2. concentrationThe mixture was concentrated
  3. stirringThe mixture was stirred overnight at 25° C.
  4. concentrationconcentrated
  5. customThe residue was purified by flash chromatography on a Biotage Horizon, 65i column
  6. washeluting with 1 column volume of 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-68e6f584be4b4d3ab84e886a5f5beb3e
Source dataset
uspto-grants-2013_05
Patent number
US08445480B2

Reaction notes

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