Triethylamine → HCID 21104323, compound

HRID 1010859Notes

Reaction equation

HRID 1010859 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-yl-amino]-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 (70 μl, 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, compound of formula (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-531c2ea0748e4787a7aa6921e7385001
Source dataset
uspto-grants-2011_07
Patent number
US07977342B2

Reaction notes

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