1211526-53-2|2-(tert-Butoxycarbonyl)-2-azaspiro[3.3]heptane-6-carboxylic acid| Ambeed

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Quality Control of [ 1211526-53-2 ] Purity: 97% SDS Specification

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Product Details of [ 1211526-53-2 ]

CAS No. :	1211526-53-2
Formula :	C₁₂H₁₉NO₄
M.W :	241.28
SMILES Code :	O=C(C(C1)CC21CN(C(OC(C)(C)C)=O)C2)O
MDL No. :	MFCD17016194
InChI Key :	SZAAHQWPPBNUQR-UHFFFAOYSA-N
Pubchem ID :	46930466

Safety of [ 1211526-53-2 ]

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

Computational Chemistry of [ 1211526-53-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	17
Num. arom. heavy atoms	0
Fraction Csp3	0.83
Num. rotatable bonds	4
Num. H-bond acceptors	4.0
Num. H-bond donors	1.0
Molar Refractivity	65.6
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	66.84 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.41
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.02
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.34
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	1.31
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	0.76
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.37

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.71
Solubility	4.66 mg/ml ; 0.0193 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.01
Solubility	2.34 mg/ml ; 0.0097 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-0.92
Solubility	29.3 mg/ml ; 0.122 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	Yes
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-7.05 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.56

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.65

Application In Synthesis of [ 1211526-53-2 ]

* 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 [ 1211526-53-2 ]

[ 1211526-53-2 ] Synthesis Path-Downstream 1~35

1
[ 1211526-53-2 ]
[ 100-51-6 ]
[ 1239589-54-8 ]

References: [1]Journal of Organic Chemistry,2010,vol. 75,p. 5941 - 5952.

2
[ 24424-99-5 ]
[ 1172252-57-1 ]
[ 1211526-53-2 ]

References: [1]Journal of Organic Chemistry,2010,vol. 75,p. 5941 - 5952.

3
[ 1211526-53-2 ]
(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]ctane-2-carbohydrazide [ No CAS ]
C₂₆H₃₅N₅O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 0℃; for 1h;	Example 40: Synthesis of(2S,5R)-2-(5-(2-azaspiro[3.3]heptan-6-yl)-l,3,4-oxadiazol-2-yl)-7- ESI-MS (EI+, m/z): 386.3.

References: [1]Patent: WO2013/149121,2013,A1 .Location in patent: Page/Page column 117.

4
[ 1211526-53-2 ]
C₂₆H₃₃N₅O₅ [ No CAS ]

References: [1]Patent: WO2013/149121,2013,A1 .

5
[ 1211526-53-2 ]
C₁₉H₂₇N₅O₅ [ No CAS ]

References: [1]Patent: WO2013/149121,2013,A1 .

6
[ 1211526-53-2 ]
(S)-tert-butyl 4-(1,2,3,4-tetrahydroisoquinoline-1-carboxamido)benzoate trifluoroacetate [ No CAS ]
[ 1598386-46-9 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 24h;	[00262] 6C. (S)-tert-Butyl 6-(l-((4-(tert-butoxycarbonyl)phenyl)carbamoyl)-l,2,3,4- tetrahydroisoquinoline-2-carbonyl)-2-azaspiro[3.3]heptane-2-carboxylate: 6B (27 mg, 0.058 mmol), <strong>[1211526-53-2]2-(tert-butoxycarbonyl)-2-azaspiro[3.3]heptane-6-carboxylic acid</strong> (13.97 mg, 0.058 mmol), EDC (11.10 mg, 0.058 mmol), and HOBT (8.86 mg, 0.058 mmol) were combined in DMF (0.8 mL) and Hunig's base (0.061 mL, 0.347 mmol) was added. After 24 h, the reaction was partitioned with water (10 mL) and ethyl acetate (10 mL). The aqueous layer was extracted with ethyl acetate(lx5 mL). The combined organic layers were washed with brine (10 mL) and dried (MgSC^) and the crude material was carried onto the next step. MS (ESI) m/z: 576.2 (M+H)+.

References: [1]Patent: WO2014/59202,2014,A1 .Location in patent: Paragraph 00262.

7
[ 1211526-53-2 ]
(S)-3-amino-3-(2-ethoxypyridin-3-yl)-1-((4-methoxyphenyl)sulfonyl)-2-oxoindoline-5-carbonitrile [ No CAS ]
N-[(3S)-5-cyano-3-(2-ethoxy-3-pyridyl)-1-(4-methoxyphenyl)sulfonyl-2-oxo-indolin-3-yl]-6-azaspiro[3.3]heptane-2-carboxamide [ No CAS ]

References: [1]Patent: US2015/344489,2015,A1 .

8
[ 1211526-53-2 ]
(S)-3-amino-3-(2-ethoxypyridin-3-yl)-1-((4-methoxyphenyl)sulfonyl)-2-oxoindoline-5-carbonitrile [ No CAS ]
(S)-tert-butyl 6-((5-cyano-3-(2-ethoxypyridin-3-yl)-1-((4-methoxyphenyl)sulfonyl)-2-oxoindolin-3-yl)carbamoyl)-2-azaspiro[3.3]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride; at 20 - 25℃; for 12h;	44.1 (S)-tert-l3utyl 6-((5-cyano-3-(2-ethoxypyridin-3-ye-i -((4-methoxyphenyl)sulfonyl)-2-oxoindolin-3-yl)carbamoyl)-2-azaspiro[3 .3]heptane-2-carboxy- late10832] Ni -((Ethylimino)methylene)-N3,N3-dimethylpro- pane-i ,3-diamine hydrochloride (5.4 mmol, 1.0 g) was added portionwise to a solution of(S)-3-amino-3-(2-ethoxypyridin- 3-ye-i -((4-methoxyphenyl)sulfonyl)-2-oxoindoline-5-car- bonitrile (1.1 mmol, 500 mg) and 2-(tert-butoxycarbonyl)-2- azaspiro[3.3]heptane-6-carboxylic acid (1.1 mmol, 260 mg) in pyridine (10 ml). The mixture was stirred for 12 hat rt. The reaction was monitoredby TLC (eluent: 5% MeOH/CH2C12). The mixture was poured onto cooled water and the precipitate filtered off. It was washed with cold water and dried in vacuo. The crude product was directly used in the next step without purification.10833] ESI-MS: [M+H]=688.20 (90% purity)

References: [1]Patent: US2015/344489,2015,A1 .Location in patent: Paragraph 0832; 0833.

9
[ 1211526-53-2 ]
N-[10,11-dichloro-4-oxo-3-(trifluoromethyl)-2,5,7-triazatricyclo[6.4.0.0²'⁶]dodeca-1⁽¹²⁾,6,8,10-tetraen-3-yl]-2-azaspiro[3.3]heptane-6-carboxamide trifluoroacetate [ No CAS ]

References: [1]Patent: WO2015/177367,2015,A1 .

10
[ 1211526-53-2 ]
tert-butyl 6-carbamoyl-2-azaspiro[3.3]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%		Intermediate 10 tert-buty 6-carbamoyl-2-azaspiro[3.3]heptane-2-carboxylate To a stirred solution of 2-[(ieri-butoxy)carbonyl]-2-azaspiro[3.3]heptane-6-carboxylic acid (700 mg, 2.90 mmol) in DCM (100 mL), under nitrogen, was added triethylamine (386 mu, 2.90 mmol). The reaction was cooled to 0C and chloro(ethoxy)methanone (304 3.19 mmol) was added dropwise. The reaction was allowed to warm to room temperature and stirred for 2 h. The reaction was then cooled to 0C and aqueous ammonia (290 muL, 2.90 mmol) was added. The reaction was allowed to warm to room temperature and stirred for 3 h. The reaction was diluted with DCM (100 mL) and washed with water (3 x 50 mL) and 10% NaHC03 (aq) (50 mL). The organic phase was dried (MgSC^), filtered and concentrated to afford the title compound as a white solid (601 mg, 86%); m z = 184.9 (MH-lBu)+.

References: [1]Patent: WO2015/177367,2015,A1 .Location in patent: Page/Page column 65.

11
[ 1211526-53-2 ]
C₁₆H₂₁F₃N₂O₅ [ No CAS ]

References: [1]Patent: WO2015/177367,2015,A1 .

12
[ 1211526-53-2 ]
tert-butyl 6-[10,11-dichloro-4-oxo-3-(trifluoromethyl)-2,5,7-triazatricyclo[6.4.0.0²'⁶]-dodeca-1⁽¹²⁾,6,8,10-tetraen-3-yl]carbamoyl}-2-azaspiro[3.3]heptane-2-carboxylate [ No CAS ]

References: [1]Patent: WO2015/177367,2015,A1 .

13
[ 1147557-97-8 ]
[ 1211526-53-2 ]

References: [1]Patent: CN105646318,2016,A .

14
[ 1374658-94-2 ]
[ 1211526-53-2 ]

Yield	Reaction Conditions	Operation in experiment
62%	With water; potassium hydroxide; In ethanol; at 20℃;	Compound 3 (2.0 g, 9.0 mmol) was dissolved in ethanol (40 mL) and water (40 mL)Potassium hydroxide (2.0 g, 36.0 mmol) was then added and stirred overnight at room temperature.TLC (petroleum ether / ethyl acetate volume ratio = 1/1, Rf = 0.0) indicated that the reaction was complete, then most of the ethanol was concentrated in vacuo, then the pH was adjusted to 3-4 with 1N hydrochloric acid and the aqueous phase extracted with dichloromethane The combined organics were dried over anhydrous sodium sulfate and concentrated in vacuo to dryness to give compound 4 (1.3 g) in 62% yield.

References: [1]Patent: CN105646318,2016,A .Location in patent: Paragraph 0009.

15
[ 1211526-53-2 ]
C₂HF₃O₂*C₉H₁₀F₃N₃O [ No CAS ]

References: [1]Patent: US2018/105491,2018,A1 .

16
[ 1211526-53-2 ]
[ 76-05-1 ]
[ 227752-10-5 ]
(S)-tert-butyl 6-((3-ethoxy-1-(6-methoxypyridin-3-yl)-3-oxopropyl)carbamoyl)-2-azaspiro[3.3]heptane-2-carboxylate trifluoroacetic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%		To a mixture of 2-(Yer/-butoxycarbonyl)-2- azaspiro[3.3]heptane-6-carboxylic acid (100 mg, 0.414 mmol) and Intermediate 11 (93 mg, 0.414 mmol) in DMF (1 niL) under Ar was added BOP (275 mg, 0.622 mmol) followed by DIPEA (0.217 mL, 1.243 mmol) . The reaction was stirred at room temperature for 1.5 h. The mixture was purified by preparative HPLC (Phenomenex Luna Axia 5mu C18 30 x 100 mm; 10 min gradient from 30% A: 70% B to 0% A: 100% B (A = 90% H2O/IO % MeOH + 0.1% TFA); (B = 90% MeOH/10% H2O + 0.1% TFA);detection at 220 nm) to yield E2A (194 mg, 83%). LCMS (ES): m/z 448.4 [M+H]+.

References: [1]Patent: WO2018/89355,2018,A1 .Location in patent: Page/Page column 94-96.

17
[ 1211526-53-2 ]
methyl (S)-3-amino-3-(3,5-dichlorophenyl)propanoate [ No CAS ]
(S)-tert-butyl 6-((1-(3,5-dichlorophenyl)-3-methoxy-3-oxopropyl)carbamoyl)-2-azaspiro[3.3]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In ethyl acetate; N,N-dimethyl-formamide; at 20℃; for 1.5h;Inert atmosphere;	To a mixture of 2-(Yer/-butoxycarbonyl)-2- azaspiro[3.3]heptane-6-carboxylic acid (50 mg, 0.207 mmol) and Intermediate 8 (51.4 mg, 0.207 mmol) in DMF (1 mL) under Ar was added TEA (0.087 mL, 0.622 mmol) followed by T3P, 50 wt% in EtOAc (0.183 mL, 0.311 mmol) . The reaction was stirred at room temperature for 1.5 h. The mixture was purified by preparative HPLC (Phenomenex Luna Axia 5mu C18 30 x 100 mm; 10 min gradient from 25% A: 75% B to 0% A: 100% B (A = 90% H2O/10% MeOH + 0.1 % TFA); (B = 90% MeOH/10% H2O + 0.1% TFA); detection at 220 nm) to yield E1A (49 mg, 50%). LCMS (ES): m/z 471.2 [M+H]+.

References: [1]Patent: WO2018/89355,2018,A1 .Location in patent: Page/Page column 92; 93.

18
[ 1211526-53-2 ]
1-phenyl-4-{6-[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]-2-azaspiro[3.3]hept-2-yl}cyclohexanecarbonitrile [ No CAS ]

References: [1]Patent: US2018/105491,2018,A1 .

19
[ 1211526-53-2 ]
[ 1272972-31-2 ]
6-tert-butyl 2-methyl 6-azaspiro[3 .4]octane-2,6-dicarboxylate [ No CAS ]
tert-butyl 6-[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]-2-azaspiro[3.3]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In tetrahydrofuran; at 20 - 80℃;	Triethylamine (1.67 mE, 12.0 mmol) and HATU (1.67 g, 4.4 mmol) were added to a solution of 2-(tert- butoxycarbonyl)-2-azaspiro[3 .3]heptane-6-carboxylic acid (0.965 g, 4.0 mmol) and 2,2,2-trifluoro-N-hydroxyethanimi- damide (0.512 g, 4.0 mmol) in THF (20 mE) and the resulting mixture was stirred at RT for 4 h then heated at reflux at 80 C. overnight. The reaction mixture was concentrated to remove the THF and the residue was partitioned between sat. aq. NaHCO3 (containing some Na2CO3) and DCM. The phases were separated and the aqueous phase was extracted further with DCM (x2). The combined organic phases were passed through a phase separator cartridge and concentrated. The crude residue was purified by flash chromatography (normal silica, mesh size: 60-120, 0% to 10% MeOH in DCM) to give impure tert-butyl 6-[3- (trifluoromethyl)-1 ,2,4-oxadiazol-5-yl]-2-azaspiro[3 .3]hep- tane-2-carboxylate (2.05 g, >100%). ECMS (Method C): mlz 278 [M-93u+H] (ESj, at1.59 mi UV active.

References: [1]Patent: US2018/105491,2018,A1 .Location in patent: Paragraph 0567; 0781; 0782; 0783; 0784.

20
[ 887144-97-0 ]
[ 1211526-53-2 ]
tert-butyl 6-(trifluoromethyl)-2-azaspiro[3.3]heptane-2-carboxylate [ No CAS ]

References: [1]Journal of the American Chemical Society,2018,vol. 140,p. 6522 - 6526.

21
[ 1211526-53-2 ]
[ 107-14-2 ]
2-(tert-butyl) 6-(cyanomethyl) 2-azaspiro[3.3]heptane-2,6-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68.9%	With triethylamine; In N,N-dimethyl-formamide; at 0℃; for 2h;	<strong>[1211526-53-2]2-(tert-butoxycarbonyl)-2-azaspiro[3.3]heptane-6-carboxylic acid</strong> (35) was synthesized by following Ref: J. Org. Chem. 2010, 75, 5941-5952. To a solution of <strong>[1211526-53-2]2-(tert-butoxycarbonyl)-2-azaspiro[3.3]heptane-6-carboxylic acid</strong> (35) (0.5 g, 2.072 mmol) in DMF (1 mL) at 0C add TEA (0.578 mL, 4.14 mmol) and chloroacetonitrile (0.131 mL, 2.072 mmol)and stir at 0C for 2h. Reaction was quenched with ice and compound was extracted with etyhlacetate(4 X 50ml).organic layer was washed with brine , Organic layer was dried over sodium sulphate and concentrated under vacuum to gave 2-tert-butyl 6-(cyanomethyl) 2-azaspiro[3.3]heptane-2,6-dicarboxylate (1p) (0.4 g, 1.427 mmol, 68.9 % yield) 1H NMR (300 MHz, CDCl3): delta 7.06 -7.03 (m,1H), 4.93 (s, 2H), 3.81-3.78 (m, 1H), 3.18-3.12 (m, 1H), 2.34-2.13 (m, 6H), 1.91-1.82 (m, 2H), 1.23 (s, 9H). MS (ESI): 298.2 as [M+H2O] in +Ve mode.

References: [1]Tetrahedron Letters,2018,p. 4267 - 4271.

22
[ 1211526-53-2 ]
tert-butyl 6-(hydroxymethyl)-2-azaspiro[3.3]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With dimethylsulfide borane complex; In tetrahydrofuran; at 0 - 65℃;Inert atmosphere;	2-(tert-Butoxycarbonyl)-2-azaspiro[3.3]heptane-6-carboxylic acid (900 mg, 3.73 mmol) was dissolved in THF (19 mL), and cooled to 0 C under an inert atmosphere. Borane dimethylsulfide complex (1.77 mL, 18.7 mmol, 2M in THF) was then added dropwise. The resulting solution was warmed to r.t. and stirred for 1 h, after which time the solution was heated to 65 C and refluxed overnight. The reaction mixture was then slowly added to a stirring solution of EtOH at 0 C and was allowed to stir for 30 min. Solvents were removed under reduced pressure, and the resulting residue was re-dissolved in DCM and washed with H2O (2x). The organic layer was concentrated to give the title compound as a colorless oil which was used without additional purification (847 mg, 100%). ES-MS [M+H]+ = 172.4 (minus t-butyl).

References: [1]Patent: WO2019/126559,2019,A1 .Location in patent: Paragraph 00221.

23
[ 1211526-53-2 ]
8-chloro-5-methyl-1-(2-azaspiro[3.3]heptan-6-yl)-5,6-dihydro-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine bis(2,2,2-trifluoroacetate) [ No CAS ]

References: [1]Patent: WO2018/226769,2018,A1 .
[2]Patent: WO2018/226769,2018,A1 .

24
[ 1211526-53-2 ]
8-chloro-1-(2-(5-fluoropyridin-2-yl)-2-azaspiro[3.3]heptan-6-yl)-5-methyl-5,6-dihydro-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepine [ No CAS ]

References: [1]Patent: WO2018/226769,2018,A1 .
[2]Patent: WO2018/226769,2018,A1 .

25
[ 1211526-53-2 ]
C₂₁H₂₂ClF₂N₅O [ No CAS ]

References: [1]Patent: WO2018/226769,2018,A1 .
[2]Patent: WO2018/226769,2018,A1 .

26
[ 1211526-53-2 ]
C₂₅H₂₇ClN₆O₂ [ No CAS ]