1,4-Dibromobutane → HCID 68033148, compound

HRID 1618328Notes

Reaction equation

HRID 1618328 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][S:5]([NH:8][C:9](=[O:40])[C:10]1[CH:15]=[CH:14][C:13]([NH:16][C:17]2[N:22]=[C:21]([NH:23][C:24]3([C:27]4[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=4)[CH2:26][CH2:25]3)[N:20]=[C:19]([O:34][CH2:35][C:36]([F:39])([F:38])[F:37])[N:18]=2)=[CH:12][CH:11]=1)(=[O:7])=[O:6].Br[CH2:42][CH2:43][CH2:44][CH2:45]Br.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.CCOC(C)=O>[Cl:33][C:30]1[CH:31]=[CH:32][C:27]([C:24]2([NH:23][C:21]3[N:20]=[C:19]([O:34][CH2:35][C:36]([F:37])([F:38])[F:39])[N:18]=[C:17]([NH:16][C:13]4[CH:12]=[CH:11][C:10]([C:9]([NH:8][S:5]([CH2:4][CH2:3][N:2]5[CH2:45][CH2:44][CH2:43][CH2:42]5)(=[O:7])=[O:6])=[O:40])=[CH:15][CH:14]=4)[N:22]=3)[CH2:26][CH2:25]2)=[CH:28][CH:29]=1

Participants

6

Reactant 3

HCID 80561,4-DibromobutaneHCID 11430Potassium CarbonateHCID 68182867HCID 68182867, compound

Product 1

HCID 68033148HCID 68033148, compoundYield 15.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of N-(2-aminoethylsulfonyl)-4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)benzamide HCl salt (20 mg, 0.031 mmol) in Acetonitrile (Volume: 2 mL) was added 1,4-dibromobutane (6.96 mg, 0.032 mmol) and POTASSIUM CARBONATE (21.23 mg, 0.154 mmol). The mixture was heated to 65° C. for 16 h. After cooling to rt, the mixture was diluted with EtOAc, washed with water, and brine. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by rev. phase preparative HPLC (Column: Sunfire prep C18 OBO 5 uM, 30×100 mm by Waters Corp) using a gradient of 20-100% ACN/water w/0.1% TFA modifier to give 4-(4-(1-(4-chlorophenyl)cyclopropylamino)-6-(2,2,2-trifluoroethoxy)-1,3,5-triazin-2-ylamino)-N-(2-(pyrrolidin-1-yl)ethylsulfonyl)benzamide (3 mg) as the TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.17-1.48 (m, 4H), 1.80-2.12 (m, 4H), 3.37-4.41 (m, 8H), 5.00 (q, J=9.0 Hz, 2H), 7.15-7.44 (m, 4H), 7.67-7.86 (m, 3H), 7.93 (s, 1H), 8.86 (br. s., 1H), 9.71 (br. s., 1H), 10.13 (br. s., 1H); LC-MS (Condition A), MS m/z (M++H) 640.0.

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with water, and brine
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified by rev

Sources & evidence

ORD record
ord-0f7b99b6497e4318823522e3fc87fa87
Source dataset
uspto-grants-2014_07
Patent number
US08765944B2

Reaction notes

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