Diisopropylethylamine → HCID 67319543, compound

HRID 899479Notes

Reaction equation

HRID 899479 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:36])([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:10][O:11][CH2:12][C:13]1[CH:14]=[C:15]([CH:19]=[C:20]([C:22]2([C:27]#[N:28])[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:21]=1)[C:16]([OH:18])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:37][C:38]1[CH:43]=[CH:42][C:41]([C@H:44]([NH2:46])[CH3:45])=[CH:40][CH:39]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C:9]([CH3:36])([CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH2:10][O:11][CH2:12][C:13]1[CH:14]=[C:15]([CH:19]=[C:20]([C:22]2([C:27]#[N:28])[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:21]=1)[C:16]([NH:46][CH:44]([C:41]1[CH:42]=[CH:43][C:38]([F:37])=[CH:39][CH:40]=1)[CH3:45])=[O:18])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 6950187(1R)-(+)-1-(4-Fluorophenyl)ethylamineHCID 67319183HCID 67319183, compound

Product 1

HCID 67319543HCID 67319543, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-((2-tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)benzoic acid (10.25 mg, 0.021 mmol), (R)-1-(4-fluorophenyl)ethanamine (0.0085 mL, 0.063 mmol), benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (12 mg, 0.025 mmol) and diisopropylethylamine (0.012 mL, 0.07 mmol) in 0.2 mL DMF was stirred at rt overnight. Purification by reverse phase preparative HPLC (5-95% MeCN/H2O containing 0.1% TFA, C18 PRO YMC 20×150 mm) gave 3-((2-tert-butoxycarbonylamino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)-N-(1-(4-fluorophenyl)ethyl)benzamide which was subsequently dissolved in 0.2 mL CH2Cl2 and 0.5 mL TFA. The reaction mixture was stirred for 1 h and concentrated. Lyophilization gave 3-((2-amino-2-methyl-3-phenylpropoxy)methyl)-5-(1-cyanocyclopentyl)-N-(1-(4-fluorophenyl)ethyl)benzamide as the TFA salt. 1H NMR (400 MHz, CD3OD) δ 8.93 (d, J=8.0 Hz, 1H), 7.92 (app d, J=1.6 Hz, 1H), 7.85 (s, 1H), 7.74 (s, 1H), 7.42 (m, 2H), 7.28 (m, 3H), 7.18 (m, 2H), 7.05 (m, 2H), 5.25 (m, 1H), 4.70 (m, 2H), 3.44 (A of AB, d, J=10.1 Hz, 1H), 3.38 (B of AB, d, J=10.1 Hz, 1H), 3.09 (d, J=13.4 Hz, 1H), 2.86 (d, J=13.4 Hz, 1H), 2.50 (m, 2H), 2.18 (m, 2H), 2.03 (m, 4H), 1.58 (d, J=7.0 Hz, 3H), 1.25 (s, 3H).

Workup

  1. customPurification by reverse phase preparative HPLC (5-95% MeCN/H2O containing 0.1% TFA

Sources & evidence

ORD record
ord-04e5f870b5b049a695ad37109fc009c9
Source dataset
uspto-grants-2008_04
Patent number
US07354942B2

Reaction notes

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