Diisopropylethylamine → HCID 131731685, compound

HRID 1628201Notes

Reaction equation

HRID 1628201 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[NH2:8][C@@H:9]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[C:10]([NH:12][C:13]1[O:17][N:16]=[C:15]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)[CH:14]=1)=[O:11].[S:32]1[CH:36]=[C:35]([CH:37]=O)[N:34]=[CH:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CCN(C(C)C)C(C)C>ClCCCl>[OH:3][C:2]([C:4]([F:7])([F:6])[F:5])=[O:1].[Cl:31][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][C@H:9]([NH:8][CH2:37][C:35]2[N:34]=[CH:33][S:32][CH:36]=2)[C:10]([NH:12][C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=3)[CH:14]=2)=[O:11])=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2763214Thiazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 86664820HCID 86664820, compound

Product 1

HCID 131731685HCID 131731685, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a 20 ml vial were added (S)-2-amino-3-(4-chlorophenyl)-N-(3-(pyridin-4-yl)isoxazol-5-yl)propanamide 3.1.C (50 mg, 0.15 mmole), thiazole-4-carbaldehyde (20 mg, 0.18 mmole), sodium triacetoxyborohydride (62 mg, 0.29 mmole), 5 ml of DCE, and DIEA (97 μl, 0.15 mmole). The reaction was stirred at 70° C. for 12 hours. The reaction was then partitioned between 10 ml of water and 20 ml of DCM and the solvent was removed by rotary evaporation. The crude was purified using reverse phase preparative HPLC to give 5.55 mg of (S)-3-(4-chlorophenyl)-N-(3-(pyridin-4-yl)isoxazol-5-yl)-2-(thiazol-4-ylmethylamino)propanamide TFA salt 3.1 as a clear film (5.6 mg, 9% yield). LCMS ESI (pos.) m/e: 440.1 (M+1): 1H NMR (500 MHz, MeOH) δ ppm 9.01 (d, J=1.71 Hz, 1H), 8.76-8.78 (m, 2H), 8.19 (d, J=6.60 Hz, 2H), 7.69 (dd, J=13.82, 8.68 Hz, 1H), 7.24 (d, J=1.96 Hz, 1H), 7.13 (d, J=8.31 Hz, 2H), 6.99 (d, J=8.31 Hz, 2H), 4.35-4.45 (s, 1H), 4.26 (m, 2H), 3.34 (dd, J=8.56, 5.87 Hz, 1H), 3.17 (dd, J=13.69, 5.87 Hz, 1H).

Workup

  1. customThe reaction was then partitioned between 10 ml of water and 20 ml of DCM
  2. customthe solvent was removed by rotary evaporation
  3. customThe crude was purified

Sources & evidence

ORD record
ord-d62d644910554cdb8cdb0ecad4ccd51c
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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