Diisopropylethylamine → HCID 131731691, compound

HRID 1628313Notes

Reaction equation

HRID 1628313 reaction equation
[OH:1][C:2]([C:4]([F:7])([F:6])[F:5])=[O:3].[NH2:8][C@@H:9]([CH2:31][C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1)[C:10]([NH:12][C:13]1[CH:14]=[C:15]([C:25]([CH3:30])([CH3:29])[C:26]([OH:28])=[O:27])[CH:16]=[C:17]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)[CH:18]=1)=[O:11].[S:39]1[CH:43]=[C:42]([CH:44]=O)[N:41]=[CH:40]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CCN(C(C)C)C(C)C.[B-]C#N.[Na+]>CO.ClCCCl>[OH:3][C:2]([C:4]([F:7])([F:6])[F:5])=[O:1].[Cl:38][C:35]1[CH:34]=[CH:33][C:32]([CH2:31][C@H:9]([NH:8][CH2:44][C:42]2[N:41]=[CH:40][S:39][CH:43]=2)[C:10]([NH:12][C:13]2[CH:14]=[C:15]([C:25]([CH3:29])([CH3:30])[C:26]([OH:28])=[O:27])[CH:16]=[C:17]([C:19]3[CH:20]=[CH:21][N:22]=[CH:23][CH:24]=3)[CH:18]=2)=[O:11])=[CH:37][CH:36]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 2763214Thiazole-4-carboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 20587905Sodium cyanoborohydride [MI]HCID 131731692HCID 131731692, compound

Product 1

HCID 131731691HCID 131731691, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a 100 ml flask were added (S)-2-(3-(2-amino-3-(4-chlorophenyl)propanamido)-5-(pyridin-4-yl)phenyl)-2-methylpropanoic acid TFA salt 63.1.C (200 mg, 0.36 mmole), thiazole-4-carbaldehyde (33 mg, 0.21 mmole), sodium triacetoxyborohydride (154 mg, 0.73 mmole), 20 ml of DCE, 1 ml MeOH and DIEA (95 μl, 0.54 mmole). The reaction was stirred at 70° C. for 2 hours at which time sodium cyanotrihydroborate (46 mg, 0.73 mmole) was added and stirred at 70° C. for an additional 1 hour. The reaction mixture was then partitioned between CH2Cl2 and water and the solvent was removed from the organic layer by rotary evaporation. The crude product was purified by reverse phase preparative HPLC to give (S)-2-(3-(3-(4-chlorophenyl)-2-(thiazol-4-ylmethylamino)propanamido)-5-(pyridin-4-yl)phenyl)-2-methylpropanoic acid TFA salt 63.1 as an off white solid (72.5 mg, 60% yield). LCMS ESI (pos.) m/e: 535.2 (M+1): 1H NMR (500 MHz, MeOH) δ ppm 9.14 (d, J=1.96 Hz, 1H), 8.79-8.91 (m, 2H), 8.14-8.25 (m, 2H), 7.99 (t, J=1.71 Hz, 1H), 7.82 (d, J=1.96 Hz, 1H), 7.69 (t, J=1.59 Hz, 1H), 7.52 (t, J=1.71 Hz, 1H), 7.35 (m, 2H), 7.27 (m, 2H), 4.43-4.63 (m, 2H), 4.28 (dd, J=9.29, 5.87 Hz, 1H), 3.45 (dd, J=13.45, 5.62 Hz, 1H), 3.24 (dd, J=13.33, 9.41 Hz, 1H), 1.65 (d, J=6.85 Hz, 6H).

Workup

  1. additionwas added
  2. customThe reaction mixture was then partitioned between CH2Cl2 and water
  3. customthe solvent was removed from the organic layer by rotary evaporation
  4. customThe crude product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-5026f33bd72b422d827177041b9c40c2
Source dataset
uspto-grants-2014_07
Patent number
US08785468B2

Reaction notes

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