Triethylamine → HCID 21104323, compound

HRID 1354326Notes

Reaction equation

HRID 1354326 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C:8]2[N:17]=[C:16]([NH:18][C:19]3[C:24]([C:25]([OH:27])=O)=[CH:23][N:22]=[CH:21][CH:20]=3)[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[N:9]=2)[CH:7]=1.C(N(CC)CC)C.[CH:36]1([NH2:39])[CH2:38][CH2:37]1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C:8]2[N:17]=[C:16]([NH:18][C:19]3[C:24]([C:25]([NH:39][CH:36]4[CH2:38][CH2:37]4)=[O:27])=[CH:23][N:22]=[CH:21][CH:20]=3)[C:15]3[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=3[N:9]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 69828CyclopropylamineHCID 2733179PyBroPHCID 21104324HCID 21104324, compound

Product 1

HCID 21104323HCID 21104323, compoundYield 34.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of 4-[2-(5-chloro-2-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-4-ylamino]-nicotinic acid (40 mg, 0.10 mmol, 1 eq) in dry DMF (1 ml) was added triethylamine (15 μl, 0.11 mmol, 1.1 eq) followed by cyclopropylamine (70μl, 0.10 mmol, 10 eq). To the suspension was added a solution of PyBrOP (56 mg, 0.21 mmol, 1.2 eq) in DMF (500 μl ) dropwise. The reaction mixture was stirred at room temperature for 16 h. The reaction was concentrated in vacuo and the residue was triturated with ether (2×20 ml). The crude residue was purified by flash column chromatography (0-5% MeOH in CHCl3) to give 4-[2-(5-Chloro-2-fluorophenyl)-5,6,7,8-tetrahydroquinazolin-4-ylamino]-N-cyclopropyl nicotinamide, 45 (15 mg, 34%) as a white solid.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe residue was triturated with ether (2×20 ml)
  3. customThe crude residue was purified by flash column chromatography (0-5% MeOH in CHCl3)

Sources & evidence

ORD record
ord-3e21e6b9dfec46febd9a5e61a01fe2ee
Source dataset
uspto-grants-2007_05
Patent number
US07223766B2

Reaction notes

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