132622-69-6|(2S,4R)-4-Amino-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid| Ambeed

CAS No. :	132622-69-6
Formula :	C₁₀H₁₈N₂O₄
M.W :	230.26
SMILES Code :	O=C([C@H]1N(C(OC(C)(C)C)=O)C[C@H](N)C1)O
MDL No. :	MFCD05664215
InChI Key :	WDWRIVZIPSHUOR-RQJHMYQMSA-N
Pubchem ID :	14842625

Safety of [ 132622-69-6 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 132622-69-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 132622-69-6 ]

[ 132622-69-6 ] Synthesis Path-Downstream 1~50

1
[ 132622-69-6 ]
[ 2651-15-2 ]
(2S,4R)-4-({Methylsulfanyl-[(E)-toluene-4-sulfonylimino]-methyl}-amino)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester [ No CAS ]

References: [1]Journal of Organic Chemistry,1991,vol. 56,p. 3009 - 3016.

2
[ 132622-68-5 ]
[ 132622-69-6 ]

References: [1]Journal of Organic Chemistry,1991,vol. 56,p. 3009 - 3016.

3
[ 132622-69-6 ]
[ 501-53-1 ]
[ 874163-00-5 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

4
[ 185304-19-2 ]
[ 132622-69-6 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.
[2]Journal of Medicinal Chemistry,2008,vol. 51,p. 1771 - 1782.

5
[ 874162-95-5 ]
[ 132622-69-6 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

6
[ 132622-69-6 ]
3(R)-[(4(R)-(4-amino)-1-(tert-butoxycarbonyl)-2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

7
[ 132622-69-6 ]
[ 874163-05-0 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

8
[ 132622-69-6 ]
[ 874163-03-8 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

9
[ 132622-69-6 ]
[ 874163-09-4 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

10
[ 132622-69-6 ]
[ 874163-10-7 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

11
[ 132622-69-6 ]
[ 874163-11-8 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

12
[ 132622-69-6 ]
3(R)-[(4(R)-(4-azidobenzoyl)amino-2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide hydrochloride [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

13
[ 132622-69-6 ]
3(R)-[(4(R)-(4-azido-2-hydroxybenzoyl)amino-2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide hydrochloride [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

14
[ 132622-69-6 ]
3(R)-[(4(R)-(4-azido-2-hydroxy-5-iodobenzoyl)amino-2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide hydrochloride [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

15
[ 89813-47-8 ]
[ 132622-69-6 ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 307 - 317.

16
[ 132622-64-1 ]
[ 132622-69-6 ]

References: [1]Journal of Organic Chemistry,1991,vol. 56,p. 3009 - 3016.

17
[ 132622-69-6 ]
[ 132622-70-9 ]

References: [1]Journal of Organic Chemistry,1991,vol. 56,p. 3009 - 3016.

18
[ 132623-04-2 ]
[ 132622-69-6 ]

References: [1]Journal of Organic Chemistry,1991,vol. 56,p. 3009 - 3016.

19
[ 37813-30-2 ]
[ 132622-69-6 ]

References: [1]Journal of Organic Chemistry,1991,vol. 56,p. 3009 - 3016.

20
[ 176486-63-8 ]
[ 132622-69-6 ]

Yield	Reaction Conditions	Operation in experiment
	With pyrrolidine; In acetonitrile; at 20℃; for 3h;	To a solution of (2S, 4R)Fmoc-4-amino-1-boc-pyrrolidine-2-carboxylic acid (400 mg, 0.884 mmol) in acetonitrile (15 mL), five drops of pyrrolidine was added. The reaction mixture was stirred at rt for 3hr. Then it was concentrated and put on high vacuum togive crude 4-amino-1-boc-pyrrolidine-2-carboxylic acid. In another round-bottomed flask, a solution ofPd2dba3 (40 mg, 5% mol) and racemic-BINAP (56 mg, 10% mol) was stirred under nitrogen in degassed toluene (8mL) at rt forlh. Then1-chloroisoquinoline (216 mg, 1.326 mmol) and sodium t-butoxide (340 mg,3.536 mmol) were added and the reaction mixture was stirred for 30 min. Then 4-amino-l-boc-pyrrolidine-2-carboxylic acid was added and the reaction mixture was heated under reflux for lh. Water was added to quench the reaction and the aqueous layer was separated and filtered through filter paper. It was then concentrated and purified by Prep. HPLC to give coupled product as TFA salt. (165 mg, 40% yield) 'H NMR(CD30D, 400 MHz)8 1.44 (m, 9H), 2.51-2. 74 (m, 2H), 3.64 (m,1H), 4.01 (m,1H), 4.49 (m,1H), 4.64 (m,1H), 7.30 (d, J=6.85 Hz,1H), 7.58 (d, J=6.85 Hz,1H), 7.79 (m,1H), 7.91-7. 99 (m, 2H), 8.56 (d, J=8. 56 Hz,1H). LC-MS (retention time: 1.707 min. ), MS m/z 358(MH+).
	With pyrrolidine; In acetonitrile; at 20℃; for 3h;	To a solution of (2S,4R) Fmoc-4-amino-1-boc-pyrrolidine-2-carboxylic acid (400 mg, 0.884 mmol) in acetonitrile (15 mL), five drops of pyrrolidine was added. The reaction mixture was stirred at rt for 3hr. Then it was concentrated and put on high vacuum to give crude 4-amino-1-boc-pyrrolidine-2-carboxylic acid. In another round-bottomed flask, a solution of Pd2dba3 (40 mg, 5% mol)and racemic-BINAP (56 mg, 10% mol) was stirred under nitrogen in degassed toluene (8 mL) at rt for 1 h. Then 1-chloroisoquinoline (216 mg, 1.326 mmol) and sodium t-butoxide (340 mg, 3.536 mmol) were added and the reaction mixture was stirred for 30 min. Then 4-amino-1-boc-pyrrolidine-2-carboxylic acid was added and the reaction mixture was heated under reflux for 1 h. Water was added to quench the reaction and the aqueous layer was separated and filtered through filter paper. It was then concentrated and purified by Prep. HPLC to give coupled product as TFA salt. (165 mg, 40% yield) 1H NMR (CD3OD, 400 MHz) δ 1.44 (m, 9H), 2.51-2.74 (m, 2H), 3.64 (m, 1H), 4.01 (m, 1H), 4.49 (m, 1H), 4.64 (m, 1H), 7.30 (d, J=6.85 Hz, 1H), 7.58 (d, J=6.85 Hz, 1H), 7.79(m, 1H), 7.91-7.99 (m, 2H), 8.56 (d, J=8.56 Hz, 1H). MS m/z 358 (MH+).
	With pyrrolidine; In acetonitrile; at 20℃; for 3h;	To a solution of (2S,4R) Fmoc-4-amino-1-boc-pyrrolidine-2-carboxylic acid (400 mg, 0.884 mmol) in acetonitrile (15 mL), five drops of pyrrolidine was added. The reaction mixture was stirred at rt for 3 hr. Then it was concentrated and put on high vacuum to give crude 4-amino-1-boc-pyrrolidine-2-carboxylic acid. In another round-bottomed flask, a solution of Pd2 dba3 (40 mg, 5% mol) and racemic-BINAP (56 mg, 10% mol) was stirred under nitrogen in degassed toluene (8 mL) at rt for 1 h. Then 1-chloroisoquinoline (216 mg, 1.326 mmol) and sodium t-butoxide (340 mg, 3.536 mmol) were added and the reaction mixture was stirred for 30 min. Then 4-amino-1-boc-pyrrolidine-2-carboxylic acid was added and the reaction mixture was heated under reflux for 1 h. Water was added to quench the reaction and the aqueous layer was separated and filtered through filter paper. It was then concentrated and purified by Prep. HPLC to give coupled product as TFA salt. (165 mg, 40% yield) 1H NMR (CD3OD, 400 MHz) δ 1.44 (m, 9H), 2.51-2.74 (m, 2H), 3.64 (m, 1H), 4.01 (m, 1H), 4.49 (m, 1H), 4.64 (m, 1H), 7.30 (d, J=6.85 Hz, 1H), 7.58 (d, J=6.85 Hz, 1H), 7.79 (m, 1H), 7.91-7.99 (m, 2H), 8.56 (d, J=8.56 Hz, 1H). MS m/z 358 (MH+).

With pyrrolidine; In acetonitrile; at 20℃; for 3h;

To a solution of (2S,4R) Fmoc-4-amino-1-boc-pyrrolidine-2-carboxylic acid (400 mg, 0.884 mmol) in acetonitrile (15 mL), five drops of pyrrolidine was added. The reaction mixture was stirred at rt for 3 hr. Then it was concentrated and put on high vacuum to give crude 4-amino-1-boc-pyrrolidine-2-carboxylic acid. In another round-bottomed flask, a solution of Pd2 dba3 (40 mg, 5% mol) and racemic-BINAP (56 mg, 10% mol) was stirred under nitrogen in degassed toluene (8 mL) at rt for 1 h. Then 1-chloroisoquinoline (216 mg, 1.326 mmol) and sodium t-butoxide (340 mg, 3.536 mmol) were added and the reaction mixture was stirred for 30 min. Then 4-amino-1-boc-pyrrolidine-2-carboxylic acid was added and the reaction mixture was heated under reflux for 1 h. Water was added to quench the reaction and the aqueous layer was separated and filtered through filter paper. It was then concentrated and purified by Prep. HPLC to give coupled product as TFA salt. (165 mg, 40% yield) 1H NMR (CD3OD, 400 MHz) δ 1.44 (m, 9H), 2.51-2.74 (m, 2H), 3.64 (m, 1H), 4.01 (m, 1H), 4.49 (m, 1H), 4.64 (m, 1H), 7.30 (d, J=6.85 Hz, 1H), 7.58 (d, J=6.85 Hz, 1H), 7.79 (m, 1H), 7.91-7.99 (m, 2H), 8.56 (d, J=8.56 Hz, 1H). MS m/z 358 (MH+).

References: [1]Patent: WO2003/99274,2003,A1 .Location in patent: Page 493-494.
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 6744 - 6751.
[3]Patent: US2007/99825,2007,A1 .Location in patent: Page/Page column 81.
[4]Patent: US2008/107623,2008,A1 .Location in patent: Page/Page column 75-76.
[5]Patent: US2008/107624,2008,A1 .Location in patent: Page/Page column 78-79.

21
trans azido acid [ No CAS ]
[ 132622-68-5 ]
[ 132622-69-6 ]
[ 132622-66-3 ]

Yield	Reaction Conditions	Operation in experiment
67%		EXAMPLE 8 STR12 (4R)-1-(tert-Butoxycarbonyl)-4-amino-L-proline (9). The trans azido acid 8b (3.0 g., 11.7 mmol) was hydrogenated as for the synthesis of 6, to give 1.8 g (67% yield) after crystlalization from ethanol, m.p.=228-229 C. (decomp.). 1 H NMR (CDCl3) δ1.42/1.47 (2s, 9H), 2.29 (m, 1H), 2.45 (m, 1H), 3.58 (m, 1H), 3.80 (m, 1H), 3.99 (m, 1H), 4.24 (m, 1H). Anal. (C10 H18 N2 O4.0.5H2 O) C, H, N.

References: [1]Patent: US5120859,1992,A .

22
[ 132622-69-6 ]
(4R)-1-(tert-Butoxycarbonyl)-4-[(p-tluenesulfonyliminoaminomethyl)amino]-L-proline [ No CAS ]
(4S)-1-(tert-Butoxycarbonyl)-4-([(p-toluenesulfonyl-iminoaminomethyl)amino]methyl)-L-proline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 9 STR13 (4R)-1-(tert-Butoxycarbonyl)-4-[(p-tluenesulfonyliminoaminomethyl)amino]-L-proline (10). The amino acid 9 (1.4 g, 6.08 mmol) was converted to 10 using the procedure for the preparation of 13. This gave 600 mg (23% yield) after crystallization from EtOAc/Etw O/hexane, m.p.=190-191 C. (decomp.). 1 H NMR (d6 DMSO) δ 1.32/1.37 (2s, 9H), 2.05 (m, 2H), 2.35 (s, 3H), 3.04 (m, 1H), 3.34 (bs, 2H), 3.53 (m, 1H), 4.11 (bs, 1H), 6.69 (bs, 1H), 7.29 (d, J=8 Hz, 2H), 7.63 (d, J=8 Hz, 2H). Anal. (C18 H26 N4 SO6) C, H, N,ΔN=-1.12%.

References: [1]Patent: US5120859,1992,A .

23
[ 132622-69-6 ]
Glycyl-[(4R)-4-[(iminoaminomethyl)amino]-L-prolyl]-glycyl-L-aspartyl-L-valine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		EXAMPLE 43 STR41 Glycyl-[(4R)-4-[(iminoaminomethyl)amino]-L-prolyl]-glycyl-L-aspartyl-L-valine. The title compound was obtained starting with the acid from Example 9 and the tripeptide resin of Example 42. The N-terminal glycine residue was coupled as in Example 42. Cleavage of the peptide from the resin and cleavage of the protective groups and purification also as described in Example 42 afforded the desired title compound. FAB mass spectrum: calc.: 500; obs.: 501 (M+1). RP-HPLC retention time: 12 min.

References: [1]Patent: US5120859,1992,A .

24
[ 82911-69-1 ]
[ 132622-69-6 ]
[ 176486-63-8 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In tetrahydrofuran; water; at 0 - 20℃; for 2h;Inert atmosphere;	To a solution of (2S,4 ?)-4-amino-l-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (30 g, 0.13 mol) in tetrahydrofuran (600 niL), aqueous sodium bicarbonate solution (Na2C03, 40 g, 0.377 mol in 240 mL H20) was added. The mixture was cooled to 0 C, and a solution of N- (9-Fluorenylmethoxycarbonyloxy)succinimide (12.3 g, 36.45 mmol) dissolved in tetrahydrofuran (20 mL) was then added. The reaction mixture was stirred for 2 h at room temperature and concentrated in vacuo to remove tetrahydrofuran. The aqueous layer was adjusted pH to 6 by hydrochloric acid (IN) and extracted with ethyl acetate and the organic layers were collected, dried over anhydrous sodium sulfate, filtered, and concentrated to afford a crude residue (2S,4 ?)- 4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-l-(ieri-butoxycarbonyl)pyrrolidine-2- carboxylic acid (59 g) which was used to the next step without further purification as a white solid. MS(ESI) m/z 353.1 [M-Boc]+

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 1771 - 1782.
[2]Patent: WO2019/28362,2019,A1 .Location in patent: Paragraph 00319; 00320; 00362; 00363.

25
[ 19493-44-8 ]
[ 132622-69-6 ]
[ 630424-18-9 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of (2S, 4R)Fmoc-4-amino-1-boc-pyrrolidine-2-carboxylic acid (400 mg, 0.884 mmol) in acetonitrile (15 mL), five drops of pyrrolidine was added. The reaction mixture was stirred at rt for 3hr. Then it was concentrated and put on high vacuum togive crude 4-amino-1-boc-pyrrolidine-2-carboxylic acid. In another round-bottomed flask, a solution ofPd2dba3 (40 mg, 5% mol) and racemic-BINAP (56 mg, 10% mol) was stirred under nitrogen in degassed toluene (8mL) at rt forlh. Then1-chloroisoquinoline (216 mg, 1.326 mmol) and sodium t-butoxide (340 mg,3.536 mmol) were added and the reaction mixture was stirred for 30 min. Then 4-amino-l-boc-pyrrolidine-2-carboxylic acid was added and the reaction mixture was heated under reflux for lh. Water was added to quench the reaction and the aqueous layer was separated and filtered through filter paper. It was then concentrated and purified by Prep. HPLC to give coupled product as TFA salt. (165 mg, 40% yield) 'H NMR(CD30D, 400 MHz)8 1.44 (m, 9H), 2.51-2. 74 (m, 2H), 3.64 (m,1H), 4.01 (m,1H), 4.49 (m,1H), 4.64 (m,1H), 7.30 (d, J=6.85 Hz,1H), 7.58 (d, J=6.85 Hz,1H), 7.79 (m,1H), 7.91-7. 99 (m, 2H), 8.56 (d, J=8. 56 Hz,1H). LC-MS (retention time: 1.707 min. ), MS m/z 358(MH+).
		To a solution of (2S,4R) Fmoc-4-amino-1-boc-pyrrolidine-2-carboxylic acid (400 mg, 0.884 mmol) in acetonitrile (15 mL), five drops of pyrrolidine was added. The reaction mixture was stirred at rt for 3hr. Then it was concentrated and put on high vacuum to give crude 4-amino-1-boc-pyrrolidine-2-carboxylic acid. In another round-bottomed flask, a solution of Pd2dba3 (40 mg, 5% mol)and racemic-BINAP (56 mg, 10% mol) was stirred under nitrogen in degassed toluene (8 mL) at rt for 1 h. Then 1-chloroisoquinoline (216 mg, 1.326 mmol) and sodium t-butoxide (340 mg, 3.536 mmol) were added and the reaction mixture was stirred for 30 min. Then 4-amino-1-boc-pyrrolidine-2-carboxylic acid was added and the reaction mixture was heated under reflux for 1 h. Water was added to quench the reaction and the aqueous layer was separated and filtered through filter paper. It was then concentrated and purified by Prep. HPLC to give coupled product as TFA salt. (165 mg, 40% yield) 1H NMR (CD3OD, 400 MHz) δ 1.44 (m, 9H), 2.51-2.74 (m, 2H), 3.64 (m, 1H), 4.01 (m, 1H), 4.49 (m, 1H), 4.64 (m, 1H), 7.30 (d, J=6.85 Hz, 1H), 7.58 (d, J=6.85 Hz, 1H), 7.79(m, 1H), 7.91-7.99 (m, 2H), 8.56 (d, J=8.56 Hz, 1H). MS m/z 358 (MH+).
		To a solution of (2S,4R) Fmoc-4-amino-1-boc-pyrrolidine-2-carboxylic acid (400 mg, 0.884 mmol) in acetonitrile (15 mL), five drops of pyrrolidine was added. The reaction mixture was stirred at rt for 3 hr. Then it was concentrated and put on high vacuum to give crude 4-amino-1-boc-pyrrolidine-2-carboxylic acid. In another round-bottomed flask, a solution of Pd2 dba3 (40 mg, 5% mol) and racemic-BINAP (56 mg, 10% mol) was stirred under nitrogen in degassed toluene (8 mL) at rt for 1 h. Then 1-chloroisoquinoline (216 mg, 1.326 mmol) and sodium t-butoxide (340 mg, 3.536 mmol) were added and the reaction mixture was stirred for 30 min. Then 4-amino-1-boc-pyrrolidine-2-carboxylic acid was added and the reaction mixture was heated under reflux for 1 h. Water was added to quench the reaction and the aqueous layer was separated and filtered through filter paper. It was then concentrated and purified by Prep. HPLC to give coupled product as TFA salt. (165 mg, 40% yield) 1H NMR (CD3OD, 400 MHz) δ 1.44 (m, 9H), 2.51-2.74 (m, 2H), 3.64 (m, 1H), 4.01 (m, 1H), 4.49 (m, 1H), 4.64 (m, 1H), 7.30 (d, J=6.85 Hz, 1H), 7.58 (d, J=6.85 Hz, 1H), 7.79 (m, 1H), 7.91-7.99 (m, 2H), 8.56 (d, J=8.56 Hz, 1H). MS m/z 358 (MH+).

With racemic-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In toluene; at 20℃; for 2.5h;Heating / reflux;

References: [1]Patent: WO2003/99274,2003,A1 .Location in patent: Page 493-494.
[2]Patent: US2007/99825,2007,A1 .Location in patent: Page/Page column 81.
[3]Patent: US2008/107623,2008,A1 .Location in patent: Page/Page column 75-76.
[4]Patent: US2008/107624,2008,A1 .Location in patent: Page/Page column 78-79.

26
[ 82911-69-1 ]
[ 132622-69-6 ]
[ 273222-05-2 ]

References: [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6744 - 6751.

27
[ 132622-69-6 ]
[ 135544-68-2 ]
C₁₄H₂₂N₂O₆ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 6744 - 6751.

28
[ 132622-69-6 ]
[ 630424-19-0 ]

References: [1]Patent: US2008/107623,2008,A1 .
[2]Patent: US2008/107624,2008,A1 .

29
[ 132622-69-6 ]
2-((2S,4R)-4-amino-1-(1,2-dimethyl-1H-imidazole-4-carbonyl)pyrrolidin-2-yl)-N-((S)-6-guanidino-1-(methylamino)-1-oxohexan-2-yl)thiazole-4-carboxamide hydrochloride salt [ No CAS ]