Cyclopropylamine → HCID 44133230, compound

HRID 336947Notes

Reaction equation

HRID 336947 reaction equation
Br[CH2:2][C:3]1[N:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:7](=[O:19])[NH:6][CH:5]([C:20]2[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][C:21]=2[S:28]([CH3:31])(=[O:30])=[O:29])[C:4]=1[C:32](OCC)=[O:33].[CH:37]1([NH2:40])[CH2:39][CH2:38]1.C(#N)C.O>C(#N)C.C(O)(C(F)(F)F)=O.C1COCC1>[CH:37]1([N:40]2[C:32](=[O:33])[C:4]3[CH:5]([C:20]4[CH:25]=[CH:24][C:23]([C:26]#[N:27])=[CH:22][C:21]=4[S:28]([CH3:31])(=[O:29])=[O:30])[NH:6][C:7](=[O:19])[N:8]([C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:16])[F:17])[CH:10]=4)[C:3]=3[CH2:2]2)[CH2:39][CH2:38]1

Participants

7

Reactant 3

HCID 69828CyclopropylamineHCID 18373917Acetonitrile--water (1/1)HCID 58133724HCID 58133724, compound

Product 1

HCID 44133230HCID 44133230, compound

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 6422Trifluoroacetic acidSolventHCID 8028TetrahydrofuranSolvent

Procedure

(rac)-Ethyl 6-(bromomethyl)-4-[4-cyano-2-(methylsulfonyl)phenyl]-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carboxylate (200 mg, 0.34 mmol; Example 13A) was dissolved in acetonitrile (5 ml), cyclopropylamine (58.4 mg, 1.02 mmol) was added and the mixture was stirred at RT overnight. The reaction mixture was then purified directly by preparative HPLC (column: Kromasil C18, 125 mm×20 mm, 5 μm, 100 Å; mobile phase A: water with 0.01% formic acid, mobile phase B acetonitrile; gradient: 0 min 10% B→2 min 10% B→9 min 90% B→12 min 90% B→12.1 min 10% B→15 min 10% B; flow rate: 0.35 ml/min; UV detection: 254 nm). The product-containing fractions were combined and once more subjected to HPLC separation [column: Sunfire C-18, 5 μm, 19 mm×150 mm; sample preparation: the sample was dissolved in 2 ml of acetonitrile+2 ml of 1% strength aqueous TFA solution+1 ml of THF; injection volume: 1000 μl; mobile phase: acetonitrile/water/1% aq. TFA 35:52:13 (0-10 min); flow rate: 25 ml/min; temperature: 40° C.; detection: 210 nm]. This gave 38 mg (22% of theory) of the title compound.

Workup

  1. customThe reaction mixture was then purified directly by preparative HPLC (column: Kromasil C18, 125 mm×20 mm, 5 μm, 100 Å; mobile phase A: water with 0.01% formic acid, mobile phase B acetonitrile; gradient: 0 min 10% B→2 min 10% B→9 min 90% B→12 min 90% B→12.1 min 10% B→15 min 10% B; flow rate: 0.35 ml/min; UV detection: 254 nm)
  2. customonce more subjected to HPLC separation [column
  3. customsample preparation
  4. custom40° C.

Sources & evidence

ORD record
ord-ca676aceff4645c1af07b7325c18fbd7
Source dataset
uspto-grants-2014_11
Patent number
US08889700B2

Reaction notes

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