Diisopropylethylamine → N1-((1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-morpholin-3-yl)propan-2-yl)-N3,N3-dipropylisophthalamide

HRID 1014879Notes

Reaction equation

HRID 1014879 reaction equation
[Si]([O:8][C@H:9]([C@H:32]1[CH2:36][C@@H:35]([O:37]CCC)[CH2:34][N:33]1C(OC(C)(C)C)=O)[C@@H:10]([NH:20][C:21](=[O:31])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28](=[O:30])[NH2:29])[CH:23]=1)[CH2:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=1)(C(C)(C)C)(C)C.[CH:48](N1CCOC[C@@H]1[C@@H](O)[C@@H](NC(=O)C1C=CC=C(C(N(CCC)CCC)=O)C=1)CC1C=C(F)C=C(F)C=1)([C:55]1C=CC=CC=1)[C:49]1C=CC=CC=1.[CH2:97](N(CCC)C(C1C=C(C=CC=1)C(O)=O)=O)[CH2:98][CH3:99].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC1C=C(CCCO)C=C(F)C=1>ClCCl>[F:19][C:14]1[CH:13]=[C:12]([CH2:11][C@H:10]([NH:20][C:21](=[O:31])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([N:29]([CH2:97][CH2:98][CH3:99])[CH2:49][CH2:48][CH3:55])=[O:30])[CH:23]=2)[C@H:9]([OH:8])[C@H:32]2[CH2:36][O:37][CH2:35][CH2:34][NH:33]2)[CH:17]=[C:16]([F:18])[CH:15]=1

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 1827693-(Dipropylcarbamoyl)benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 140499113-(3,5-Difluorophenyl)propan-1-olHCID 67315032(2R,4R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-2-(3-(carbamoyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylateHCID 68497146N1-((1S,2S)-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamide

Product 1

HCID 11848527N1-((1S,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((R)-morpholin-3-yl)propan-2-yl)-N3,N3-dipropylisophthalamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Step 5 (A): N1-((1S,2S)-1-((R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamide. To a solution of 3-(dipropylcarbamoyl)benzoic acid (Preparation E, 14 mg, 0.055 mmol) in dichloromethane (1 mL) was added Hunig's base (18 mg, 0.14 mmol) to make a clear solution and HATU (25 mg, 0.064 mmol) was then added. After stirring for 20 min, the reaction mixture was added (1S,2S)-2-amino-14R)-4-benzhydrylmorpholin-3-yl)-3-(3,5-difluorophenyl)propan-1-ol (Preparation D, (20 mg, 0.046 mmol) and the reaction mixture was stirred at rt overnight. Dichloromethane (100 mL) was added and washed with H2O (50 mL) twice, dried over Na2SO4, and concentrated to give the title compound as a crude product ready for next step without purification: 1H NMR (CD3OD, 500 MHz) δ 0.71 (3H, m), 1.01 (3H, m), 1.52 (2H, m), 1.74 (2H, m), 2.52 (1H, d, J=5 Hz), 2.63 (2H, dd, J=5, 15 Hz), 2.71 (1H, m), 3.12-3.19 (3H, m), 3.44-3.49 (3H, m), 3.94-3.99 (2H, m), 4.04 (1H, m), 4.58 (1H, m), 5.06 (1H, m), 5.50 (1H, s), 6.76 (1H, m), 6.92-6.95 (2H, m), 7.14-7.19 (3H, m), 7.25-7.32 (3H, m), 7.44 (2H, m), 7.49-7.55 (2H, m), 7.58 (2H, d, J=10 Hz), 7.63 (1H, s), 7.73-7.76 (1H, m).

Workup

  1. additionwas then added
  2. customPreparation D, (20 mg, 0.046 mmol)
  3. stirringthe reaction mixture was stirred at rt overnight
  4. washwashed with H2O (50 mL) twice
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-d559d549227c42c6b88a05be8c8b1e30
Source dataset
uspto-grants-2011_07
Patent number
US07981913B2

Reaction notes

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